Skip to main content
Log in

Impact of calcific aortic valve disease on valve mechanics

  • Review Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

The aortic valve is a highly dynamic structure characterized by a transvalvular flow that is unsteady, pulsatile, and characterized by episodes of forward and reverse flow patterns. Calcific aortic valve disease (CAVD) resulting in compromised valve function and increased pressure overload on the ventricle potentially leading to heart failure if untreated, is the most predominant valve disease. CAVD is a multi-factorial disease involving molecular, tissue and mechanical interactions. In this review, we aim at recapitulating the biomechanical loads on the aortic valve, summarizing the current and most recent research in the field in vitro, in-silico, and in vivo, and offering a clinical perspective on current strategies adopted to mitigate or approach CAVD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

TrAV:

Tricuspid aortic valve

TAVR:

Transcatheter aortic valve replacement

AS:

Aortic stenosis

WSS:

Wall shear stress

AWSS:

Average wall shear stress

BAV:

Bicuspid aortic valve

CAVD:

Calcific aortic valve disease

VEC:

Valvular endothelial cells

VIC:

Valvular interstitial cells

SMC:

Smooth muscle cells

BMP:

Bone morphogenetic protein

LDV:

Laser doppler velocimetry

CFD:

Computational fluid dynamics

FSI:

Fluid structure interaction

TPG:

Transvalvular pressure gradient

CT:

Computed tomography

HU:

Hounsfield units

References

  • Aikawa E, Otto CM (2012) Look more closely at the valve: imaging calcific aortic valve disease. Circulation. https://doi.org/10.1161/CIRCULATIONAHA.111.073452

  • Amindari A, Saltik L, Kirkkopru K, Yacoub M, Yalcin HC (2017) Assessment of calcified aortic valve leaflet deformations and blood flow dynamics using fluid-structure interaction modeling. Inform Med Unlocked 9:191–199

    Google Scholar 

  • Andreas B, Darren M, David H-S, Simon K, Michael J, Krzysztof B, Jaroslaw T, Rotem H, Yael K, Lena P, Peter A (2021) Non-implant valve repair for calcific aortic stenosis: the Leaflex study. EuroIntervention 16(16):1366–1369

    Google Scholar 

  • Arjunon S, Rathan S, Jo H, Yoganathan AP (2013) Aortic valve: mechanical environment and mechanobiology. Ann Biomed Eng 41(7):1331–1346

    Google Scholar 

  • Aronow WS (2018) Hypertension, aortic stenosis, and aortic regurgitation. Ann Transl Med 6(3):43

    Google Scholar 

  • Arzani A, Mofrad MRK (2017) A strain-based finite element model for calcification progression in aortic valves. J Biomech 65:216–220

    Google Scholar 

  • Atkins SK, Moore AN, Sucosky P (2016) WJC. World 8(1):89–97

    Google Scholar 

  • Basri AA, Zuber M, Zakaria MS, Illyani E, Ahmad A. The effects of aortic stenosis on the hemodynamic flow properties using computational fluid dynamics. In Proc Int Conf Comput Methods Eng Heal Sci(ICCMEH), December 2016 Sep, pp 17–19

  • Bahlmann E, Cramariuc D, Gerdts E, Gohlke-Baerwolf C, Nienaber CA, Eriksen E, Wachtell K, Chambers J, Kuck KH, Ray S (2010) Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy. JACC Cardiovasc Imaging 3(6):555–562

    Google Scholar 

  • Bahlmann E, Gerdts E, Cramariuc D, Gohlke-Baerwolf C, Nienaber CA, Wachtell K, Seifert R, Chambers JB, Kuck KH, Ray S (2013) Prognostic value of energy loss index in asymptomatic aortic stenosis. Circulation 127(10):1149–1156

    Google Scholar 

  • Bahrami S, Firouzi F (2016) The effect of wall shear stress and oscillatory shear index on probability of atherosclerosis plaque formation in normal left coronary artery tree. Iranian J Biomed Eng 9(3):293–303

  • Balachandran K, Sucosky P, Jo H, Yoganathan AP (2010) Elevated cyclic stretch induces aortic valve calcification in a bone morphogenic protein-dependent manner. Am J Pathol 177(1):49–57

    Google Scholar 

  • Barker AJ, Markl M (2011) The role of hemodynamics in bicuspid aortic valve disease. Oxford University Press for the European Association for Cardio-Thoracic Surgery and the European Society of Thoracic Surgeons, Germany

    Google Scholar 

  • Barker AJ, Markl M, Bürk J, Lorenz R, Bock J, Bauer S, Schulz-Menger J, von Knobelsdorff-Brenkenhoff F (2012) Bicuspid aortic valve is associated with altered wall shear stress in the ascending aorta. Circ Cardiovasc Imaging 5(4):457–466

    Google Scholar 

  • Bauer M, Siniawski H, Pasic M, Schaumann B, Hetzer R (2006) Different hemodynamic stress of the ascending aorta wall in patients with bicuspid and tricuspid aortic valve. J Card Surg 21(3):218–220

    Google Scholar 

  • Baumgartner H, Hung J, Bermejo J, Chambers JB, Edvardsen T, Goldstein S, Lancellotti P, LeFevre M, Miller F Jr, Otto CM (2017) Recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography. Eur Heart J Cardiovasc Imaging 18(3):254–275

    Google Scholar 

  • Bouchareb R, Boulanger M-C, Tastet L, Mkannez G, Nsaibia MJ, Hadji F, Dahou A, Messadeq Y, Arsenault BJ, Pibarot P (2019) Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis. Eur Heart J 40(17):1362–1373

    Google Scholar 

  • Bouchareb R, Guauque-Olarte S, Snider J, Zaminski D, Anyanwu A, Stelzer P, Lebeche D (2021) Proteomic architecture of valvular extracellular matrix: FNDC1 and MXRA5 are new biomarkers of aortic stenosis. Basic Transl Sci 6(1):25–39

    Google Scholar 

  • Cao K, Bukač M, Sucosky P (2016) Three-dimensional macro-scale assessment of regional and temporal wall shear stress characteristics on aortic valve leaflets. Comput Methods Biomech Biomed Engin 19(6):603–613

    Google Scholar 

  • Chandra S, Rajamannan NM, Sucosky P (2012) Computational assessment of bicuspid aortic valve wall-shear stress: implications for calcific aortic valve disease. Biomech Model Mechanobiol 11(7):1085–1096

    Google Scholar 

  • Chandran KB, Rittgers SE, Yoganathan AP (2012) Biofluid mechanics: the human circulation. CRC Press, Boca Raton

    Google Scholar 

  • Chen Y, Luo H (2020) Pressure distribution over the leaflets and effect of bending stiffness on fluid–structure interaction of the aortic valve. J Fluid Mech. https://doi.org/10.1017/jfm.2019.904

    Article  MathSciNet  MATH  Google Scholar 

  • Clavel M-A, Ennezat PV, Maréchaux S, Dumesnil JG, Capoulade R, Hachicha Z, Mathieu P, Bellouin A, Bergeron S, Meimoun P (2013) Stress echocardiography to assess stenosis severity and predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis and preserved LVEF. JACC Cardiovasc Imaging 6(2):175–183

    Google Scholar 

  • Côté N, El Husseini D, Pépin A, Guauque-Olarte S, Ducharme V, Bouchard-Cannon P, Audet A, Fournier D, Gaudreault N, Derbali H, McKee MD, Simard C, Després J-P, Pibarot P, Bossé Y, Mathieu P (2012) ATP acts as a survival signal and prevents the mineralization of aortic valve. J Mol Cell Cardiol 52(5):1191–1202

    Google Scholar 

  • Coté N, Mahmut A, Bosse Y, Couture C, Pagé S, Trahan S, Boulanger M-C, Fournier D, Pibarot P, Mathieu P (2013) Inflammation is associated with the remodeling of calcific aortic valve disease. Inflammation 36(3):573–581

    Google Scholar 

  • De Wilde D, Trachet B, De Meyer GR, Segers P (2016) Shear stress metrics and their relation to atherosclerosis: an in vivo follow-up study in atherosclerotic mice. Ann Biomed Eng 44(8):2327–2338

    Google Scholar 

  • Demer LL, Tintut Y (2014) Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arterioscler Thromb Vasc Biol 34(4):715–723

    Google Scholar 

  • Drolet M-C, Arsenault M, Couet J (2003) Experimental aortic valve stenosis in rabbits. J Am Coll Cardiol 41(7):1211–1217

    Google Scholar 

  • Drolet M-C, Roussel E, Deshaies Y, Couet J, Arsenault M (2006) A high fat/high carbohydrate diet induces aortic valve disease in C57BL/6J mice. J Am Coll Cardiol 47(4):850–855

    Google Scholar 

  • Dumont K, Vierendeels J, Verdonck P (2003) Shear stress on aortic valve leaflets using a fluid-structure interaction model of a heart valve. ASAIO J 49(2):209

    Google Scholar 

  • Dutta P, Lincoln J (2018) Calcific aortic valve disease: a developmental biology perspective. Curr Cardiol Rep 20(4):1–13

    Google Scholar 

  • El Husseini D, Boulanger M-C, Mahmut A, Bouchareb R, Laflamme M-H, Fournier D, Pibarot P, Bossé Y, Mathieu P (2014) P2Y2 receptor represses IL-6 expression by valve interstitial cells through Akt: implication for calcific aortic valve disease. J Mol Cell Cardiol 72:146–156

    Google Scholar 

  • Falahatpisheh A, Morisawa D, Toosky TT, Kheradvar A (2017) A calcified polymeric valve for valve-in-valve applications. J Biomech 50:77–82

    Google Scholar 

  • Farber G, Buchler A, Munch M, Messika-Zeitoun D, Rotstein B (2020) Multimodality imaging to predict calcific aortic valve disease progression in animal models. J Nuclear Med 61(supplement 1):27

  • Fernández B, Soto-Navarrete MT, López-García A, López-Unzu M, Durán AC, Fernández MC (2020) Bicuspid aortic valve in 2 model species and review of the literature. Vet Pathol 57(2):321–331

    Google Scholar 

  • Fisher CI, Chen J, Merryman WD (2013) Calcific nodule morphogenesis by heart valve interstitial cells is strain dependent. Biomech Model Mechanobiol 12(1):5–17

    Google Scholar 

  • Flemister DC, Hatoum H, Guhan V, Zebhi B, Lincoln J, Crestanello J, Dasi LP (2020) Effect of left and right coronary flow waveforms on aortic sinus hemodynamics and leaflet shear stress: correlation with calcification locations. Ann Biomed Eng 48(12):2796–2808

    Google Scholar 

  • Fletcher AJ, Sellers SL (2021) Aortic stenosis: is extracellular matrix the answer? American College of Cardiology Foundation, Washington DC

    Google Scholar 

  • Frigiola A, Sophocleous F, Biglino G (2021) Aortic disease: bicuspid aortic valve, aortic coarctation, marfan syndrome. In: Multimodality imaging innovations in adult congenital heart disease, Springer, Cham, pp 243–273

  • Garcia D, Pibarot P, Dumesnil JG, Sakr F, Durand L-G (2000) Assessment of aortic valve stenosis severity: a new index based on the energy loss concept. Circulation 101(7):765–771

    Google Scholar 

  • Garcia D, Pibarot P, Durand L-G (2005) Analytical modeling of the instantaneous pressure gradient across the aortic valve. J Biomech 38(6):1303–1311

    Google Scholar 

  • Garcia D, Kadem L, Savéry D, Pibarot P, Durand L-G (2006) Analytical modeling of the instantaneous maximal transvalvular pressure gradient in aortic stenosis. J Biomech 39(16):3036–3044

    Google Scholar 

  • Garcia J, Barker AJ, Murphy I, Jarvis K, Schnell S, Collins JD, Carr JC, Malaisrie SC, Markl M (2016) Four-dimensional flow magnetic resonance imaging-based characterization of aortic morphometry and haemodynamics: impact of age, aortic diameter, and valve morphology. Eur Heart J Cardiovasc Imaging 17(8):877–884

    Google Scholar 

  • Généreux P, Pibarot P, Redfors B, Mack MJ, Makkar RR, Jaber WA, Svensson LG, Kapadia S, Tuzcu EM, Thourani VH, Babaliaros V, Herrmann HC, Szeto WY, Cohen DJ, Lindman BR, McAndrew T, Alu MC, Douglas PS, Hahn RT, Kodali SK, Smith CR, Miller DC, Webb JG, Leon MB (2017) Staging classification of aortic stenosis based on the extent of cardiac damage. Eur Heart J 38(45):3351–3358

    Google Scholar 

  • Gittenberger-de Groot AC, Bartelings MM, Holman ER, Klautz RJ, Schalij MJ, Jongbloed MR (2018) The extent of the raphe in bicuspid aortic valves is associated with aortic regurgitation and aortic root dilatation. Bicuspid Aortic Valve Dis 24(2):19

    Google Scholar 

  • Gnyaneshwar R, Kumar RK, Balakrishnan KR (2002) Dynamic analysis of the aortic valve using a finite element model. Ann Thorac Surg 73(4):1122–1129

    Google Scholar 

  • Gomel MA, Lee R, Grande-Allen KJ (2019) Comparing the role of mechanical forces in vascular and valvular calcification progression. Front Cardiovasc Med 5:197

    Google Scholar 

  • Grossman W, Jones D, McLaurin LP (1975) Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Investig 56(1):56–64

    Google Scholar 

  • Guzzardi DG, Barker AJ, Van Ooij P, Malaisrie SC, Puthumana JJ, Belke DD, Mewhort HE, Svystonyuk DA, Kang S, Verma S (2015) Valve-related hemodynamics mediate human bicuspid aortopathy: insights from wall shear stress mapping. J Am Coll Cardiol 66(8):892–900

    Google Scholar 

  • Halevi R, Hamdan A, Marom G, Mega M, Raanani E, Haj-Ali R (2015) Progressive aortic valve calcification: three-dimensional visualization and biomechanical analysis. J Biomech 48(3):489–497

    Google Scholar 

  • Halevi R, Hamdan A, Marom G, Lavon K, Ben-Zekry S, Raanani E, Bluestein D, Haj-Ali R (2016) Fluid–structure interaction modeling of calcific aortic valve disease using patient-specific three-dimensional calcification scans. Med Biol Eng Comput 54(11):1683–1694

    Google Scholar 

  • Halevi R, Hamdan A, Marom G, Lavon K, Ben-Zekry S, Raanani E, Haj-Ali R (2018) A new growth model for aortic valve calcification. J Biomech Eng 10(1115/1):4040338

    Google Scholar 

  • Hasler D, Obrist D (2018) Three-dimensional flow structures past a bio-prosthetic valve in an in-vitro model of the aortic root. PloS one 13(3):e0194384

    Google Scholar 

  • Hatoum H, Dasi LP (2018) Sinus hemodynamics in representative stenotic native bicuspid and tricuspid aortic valves: an in-vitro study. Fluids 3(3):56

    Google Scholar 

  • Hatoum H, Dasi LP (2019) Spatiotemporal complexity of the aortic sinus vortex as a function of leaflet calcification. Ann Biomed Eng 47(4):1116–1128

    Google Scholar 

  • Hatoum H, Moore BL, Maureira P, Dollery J, Crestanello JA, Dasi LP (2017) Aortic sinus flow stasis likely in valve-in-valve transcatheter aortic valve implantation. J Thorac Cardiovasc Surg 154(1):32-43. e31

    Google Scholar 

  • Hatoum H, Moore BL, Dasi LP (2018) On the significance of systolic flow waveform on aortic valve energy loss. Ann Biomed Eng 46(12):2102–2111

    Google Scholar 

  • Hatoum H, Maureira P, Lilly S, Dasi LP (2019a) Impact of leaflet laceration on transcatheter aortic valve-in-valve washout: BASILICA to solve neosinus and sinus stasis. JACC Cardiovasc Interv 12(13):1229–1237

    Google Scholar 

  • Hatoum H, Maureira P, Lilly S, Dasi LP (2019b) Leaflet laceration to improve neosinus and sinus flow after valve-in-valve. Circ Cardiovasc Interv 12(3):e007739

    Google Scholar 

  • Hatoum H, Mo X-M, Crestanello JA, Dasi LP (2019c) Modeling of the instantaneous transvalvular pressure gradient in aortic stenosis. Ann Biomed Eng 47(8):1748–1763

    Google Scholar 

  • Hatoum H, Maureira P, Lilly S, Dasi LP (2020) Impact of BASILICA on sinus and neo-sinus hemodynamics after valve-in-valve with and without coronary flow. Cardiovasc Revasc Med 21(3):271–276

    Google Scholar 

  • Hatoum H, Gooden S, Sathananthan J, Lilly S, Ihdayhid Abdul R, Thourani V, Dasi Lakshmi P (2021) Sinus and neo-sinus flow evaluation after implantation of an evolut, SAPIEN 3, accurate neo and Allegra transcatheter valves. J Am Coll Cardiol 77(18_Supplement_1):1708–1708

    Google Scholar 

  • Helske S, Kupari M, Lindstedt KA, Kovanen PT (2007) Aortic valve stenosis: an active atheroinflammatory process. Curr Opin Lipidol 18(5):483–491

    Google Scholar 

  • Hope MD, Hope TA, Meadows AK, Ordovas KG, Urbania TH, Alley MT, Higgins CB (2010) Bicuspid aortic valve: four-dimensional MR evaluation of ascending aortic systolic flow patterns. Radiology 255(1):53–61

    Google Scholar 

  • Hope MD, Urbania TH, John-Paul JY, Chitsaz S, Tseng E (2012) Incidental aortic valve calcification on CT scans: significance for bicuspid and tricuspid valve disease. Acad Radiol 19(5):542–547

    Google Scholar 

  • Hope MD, Sigovan M, Wrenn SJ, Saloner D, Dyverfeldt P (2014) MRI hemodynamic markers of progressive bicuspid aortic valve-related aortic disease. J Magn Reson Imaging 40(1):140–145

    Google Scholar 

  • Hsu C-PD, Hutcheson JD, Ramaswamy S (2020) Oscillatory fluid-induced mechanobiology in heart valves with parallels to the vasculature. Vasc Biol 2(1):R59–R71

    Google Scholar 

  • Hutcheson JD, Aikawa E, Merryman WD (2014) Potential drug targets for calcific aortic valve disease. Nat Rev Cardiol 11(4):218

    Google Scholar 

  • Impiombato AN, La Civita G, Orlandi F, Franceschini Zinani FS, Oliveira Rocha LA, Biserni C (2021) A simple transient Poiseuille-based approach to mimic the Womersley function and to model pulsatile blood flow. Dynamics 1(1):9–17

    Google Scholar 

  • Jander N, Hochholzer W, Kaufmann BA, Bahlmann E, Gerdts E, Boman K, Chambers JB, Nienaber CA, Ray S, Rossebo A (2014) Velocity ratio predicts outcomes in patients with low gradient severe aortic stenosis and preserved EF. Heart 100(24):1946–1953

    Google Scholar 

  • Jermihov PN, Jia L, Sacks MS, Gorman RC, Gorman JH, Chandran KB (2011) Effect of geometry on the leaflet stresses in simulated models of congenital bicuspid aortic valves. Cardiovasc eng tech 2(1):48–56

  • Jhun C-S, Newswanger R, Cysyk JP, Ponnaluri S, Good B, Manning KB, Rosenberg G (2021) Dynamics of blood flows in aortic stenosis: mild, moderate, and severe. ASAIO J 67(6):666–674

    Google Scholar 

  • Kadem L, Dumesnil JG, Rieu R, Durand LG, Garcia D, Pibarot P (2005) Impact of systemic hypertension on the assessment of aortic stenosis. Heart 91(3):354–361

    Google Scholar 

  • Kamperidis V, Delgado V, van Mieghem NM, Kappetein AP, Leon MB, Bax JJ (2016) Diagnosis and management of aortic valve stenosis in patients with heart failure. Eur J Heart Fail 18(5):469–481

    Google Scholar 

  • Khan SU, Riaz H, Khan MU, Zarak MS, Khan MZ, Khan MS, Sattur S, Desai MY, Kaluski E, Alkhouli M (2019) Meta-analysis of temporal and surgical risk dependent associations with outcomes after transcatheter versus surgical aortic valve implantation. Am J Cardiol 124(10):1608–1614

    Google Scholar 

  • Kivi AR, Sedaghatizadeh N, Cazzolato BS, Zander AC, Roberts-Thomson R, Nelson AJ, Arjomandi M (2020) Fluid structure interaction modelling of aortic valve stenosis: effects of valve calcification on coronary artery flow and aortic root hemodynamics. Comput Methods Progr Biomed 196:105647

    Google Scholar 

  • Kostyunin AE, Yuzhalin AE, Ovcharenko EA, Kutikhin AG (2019) Development of calcific aortic valve disease: do we know enough for new clinical trials? J Mol Cell Cardiol 132:189–209

    Google Scholar 

  • Kwon HM, Lee BK, Kim D, Hong BK, Byun KH, Kna JS, Kim IJ, Oh SH, Kim HS (1998) Experimental hypercholesterolemia induces ultrastructural changes in the elastic laminae of rabbit aortic valve. Yonsei Med J 39(4):345–354

    Google Scholar 

  • Lerman DA, Prasad S, Alotti N (2015) Calcific aortic valve disease: molecular mechanisms and therapeutic approaches. Eur Cardiol Rev 10(2):108

    Google Scholar 

  • Lindman BR, Clavel M-A, Mathieu P, Iung B, Lancellotti P, Otto CM, Pibarot P (2016) Calcific aortic stenosis. Nat Rev Dis Primers 2(1):1–28

    Google Scholar 

  • Liu X, He Y, Zhu Q, Gao F, He W, Yu L, Zhou Q, Kong M, Wang J (2018) Supra-annular structure assessment for self-expanding transcatheter heart valve size selection in patients with bicuspid aortic valve. Catheter Cardiovasc Interv 91(5):986–994

    Google Scholar 

  • LlNDROOS M, Kupari M, Valvanne J, Strandberg T, Heikkilä J, TlLVIS R (1994) Factors associated with calcific aortic valve degeneration in the elderly. Eur Heart J 15(7):865–870

    Google Scholar 

  • Madukauwa-David ID, Sadri V, Kamioka N, Midha PA, Raghav V, Oshinski JN, Sharma R, Babaliaros V, Yoganathan AP (2020) Transcatheter aortic valve deployment influences neo-sinus thrombosis risk: an in vitro flow study. Catheter Cardiovasc Interv 95(5):1009–1016

    Google Scholar 

  • Mahadevia R, Barker AJ, Schnell S, Entezari P, Kansal P, Fedak PW, Malaisrie SC, McCarthy P, Collins J, Carr J (2014) Bicuspid aortic cusp fusion morphology alters aortic three-dimensional outflow patterns, wall shear stress, and expression of aortopathy. Circulation 129(6):673–682

    Google Scholar 

  • Manno G, Bentivegna R, Morreale P, Nobile D, Santangelo A, Novo S, Novo G (2019) Chronic inflammation: a key role in degeneration of bicuspid aortic valve. J Mol Cell Cardiol 130:59–64

    Google Scholar 

  • Marom G, Kim H-S, Rosenfeld M, Raanani E, Haj-Ali R (2013a) Fully coupled fluid–structure interaction model of congenital bicuspid aortic valves: effect of asymmetry on hemodynamics. Med Biol Eng Comput 51(8):839–848

    Google Scholar 

  • Marom G, Peleg M, Halevi R, Rosenfeld M, Raanani E, Hamdan A, Haj-Ali R (2013b) Fluid-structure interaction model of aortic valve with porcine-specific collagen fiber alignment in the cusps. J Biomech Eng 135(10):101001

    Google Scholar 

  • Martin C, Sun W (2012) Biomechanical characterization of aortic valve tissue in humans and common animal models. J biomed mat res Part A 100(6):1591–1599

  • McBride KL, Riley MF, Zender GA, Fitzgerald-Butt SM, Towbin JA, Belmont JW, Cole SE (2008) NOTCH1 mutations in individuals with left ventricular outflow tract malformations reduce ligand-induced signaling. Hum Mol Genet 17(18):2886–2893

    Google Scholar 

  • Michael J, Yoseph R, Yaron M, Ashraf H, Yael K, Nitzan T, Sharon S, Dror T, Erez G, Ehud R (2015) The LeaflexTM Catheter system—a viable treatment option alongside valve replacement? Preclinical feasibility of a novel device designed for fracturing aortic valve calcification. EuroIntervention 11(5):582–590

    Google Scholar 

  • Monin J-L, Lancellotti P, Monchi M, Lim P, Weiss E, Piérard L, Guéret P (2009) Risk score for predicting outcome in patients with asymptomatic aortic stenosis. Circulation 120(1):69–75

    Google Scholar 

  • Moore BL (2015) Influence of anatomic valve conditions and coronary flow on aortic sinus hemodynamics, Colorado State University

  • Moore BL, Dasi LP (2015) Coronary flow impacts aortic leaflet mechanics and aortic sinus hemodynamics. Ann Biomed Eng 43(9):2231–2241

    Google Scholar 

  • Morvan M, Arangalage D, Franck G, Perez F, Cattan-Levy L, Codogno I, Jacob-Lenet M-P, Deschildre C, Choqueux C, Even G (2019) Relationship of iron deposition to calcium deposition in human aortic valve leaflets. J Am Coll Cardiol 73(9):1043–1054

    Google Scholar 

  • Myles V, Liao J, Warnock JN (2014) Cyclic pressure and angiotensin II influence the biomechanical properties of aortic valves. J Biomech Eng 136(1):011011

    Google Scholar 

  • Ncho B, Sadri V, Ortner J, Kollapaneni S, Yoganathan A (2021) In-vitro assessment of the effects of transcatheter aortic valve leaflet design on neo-sinus geometry and flow. Ann Biomed Eng 49(3):1046–1057

    Google Scholar 

  • Nigam V, Srivastava D (2009) Notch1 represses osteogenic pathways in aortic valve cells. J Mol Cell Cardiol 47(6):828–834

    Google Scholar 

  • Olsson M, Rosenqvist M, Nilsson J (1994) Expression of HLA-DR antigen and smooth muscle cell differentiation markers by valvular fibroblasts in degenerative aortic stenosis. J Am Coll Cardiol 24(7):1664–1671

    Google Scholar 

  • Osman M, Ghaffar YA, Foster T, Osman K, Alqahtani F, Shah K, Kheiri B, Alkhouli M (2019) Meta-analysis of outcomes of transcatheter aortic valve implantation among patients with low gradient severe aortic stenosis. Am J Cardiol 124(3):423–429

    Google Scholar 

  • Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O’Gara PT, Rigolin VH, Sundt TM 3rd, Thompson A, Toly C (2021) 2020 ACC/AHA guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 77(4):450–500

    Google Scholar 

  • Patel KV, Omar W, Gonzalez PE, Jessen ME, Huffman L, Kumbhani DJ, Bavry AA (2020) Expansion of TAVR into low-risk patients and who to consider for SAVR. Cardiology and Therapy pp 377––394

  • Pawade T, Clavel M-A, Tribouilloy C, Dreyfus J, Mathieu T, Tastet L, Renard C, Gun M, Jenkins WSA, Macron L (2018) Computed tomography aortic valve calcium scoring in patients with aortic stenosis. Circ Cardiovasc Imaging 11(3):e007146

    Google Scholar 

  • Pibarot P, Dumesnil JG (2012) Low-flow, low-gradient aortic stenosis with normal and depressed left ventricular ejection fraction. J Am Coll Cardiol 60(19):1845–1853

    Google Scholar 

  • Pibarot P, Garcia D, Dumesnil JG (2013) Energy loss index in aortic stenosis: from fluid mechanics concept to clinical application. Circulation 127(10):1101–1104

  • Pott D, Sedaghat A, Schmitz C, Werner N, Schmitz-Rode T, Steinseifer U, Jansen SV (2021) Hemodynamics inside the neo- and native sinus after TAVR: effects of implant depth and cardiac output on flow field and coronary flow. Artif Organs 45(1):68–78

    Google Scholar 

  • Qin T, Caballero A, Mao W, Barrett B, Kamioka N, Lerakis S, Sun W (2020) The role of stress concentration in calcified bicuspid aortic valve. J R Soc Interface 17(167):20190893

    Google Scholar 

  • Raghav V, Barker AJ, Mangiameli D, Mirabella L, Markl M, Yoganathan AP (2018) Valve mediated hemodynamics and their association with distal ascending aortic diameter in bicuspid aortic valve subjects. J Magn Reson Imaging 47(1):246–254

    Google Scholar 

  • Rahman O, Scott M, Bollache E, Suwa K, Collins J, Carr J, Fedak P, McCarthy P, Malaisrie C, Barker AJ (2019) Interval changes in aortic peak velocity and wall shear stress in patients with bicuspid aortic valve disease. Int J Cardiovasc Imaging 35(10):1925–1934

    Google Scholar 

  • Ranga A, Mongrain R, Biadilah Y, Cartier R, Mcgill M (2007) A compliant dynamic FEA model of the aortic valve. In: 12th IFToMM World Congress, Besancon (France)

  • Rego BV, Sacks MS (2017) A functionally graded material model for the transmural stress distribution of the aortic valve leaflet. J biomech 54:88–95

  • Rementer CW, Wu M, Buranaphatthana W, Yang H-YL, Scatena M, Giachelli CM (2013) An inducible, ligand-independent receptor activator of NF-κB gene to control osteoclast differentiation from monocytic precursors. PloS one 8(12):e84465

    Google Scholar 

  • Roberts WC, Ko JM (2005) 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 111(7):920–925

    Google Scholar 

  • Robicsek F, Thubrikar MJ, Cook JW, Fowler B (2004) The congenitally bicuspid aortic valve: how does it function? Why does it fail? Ann Thorac Surg 77(1):177–185

    Google Scholar 

  • Sadrabadi MS, Hedayat M, Borazjani I, Arzani A (2021) Fluid-structure coupled biotransport processes in aortic valve disease. J Biomech 117:110239

    Google Scholar 

  • Saikrishnan N, Yap C-H, Milligan NC, Vasilyev NV, Yoganathan AP (2012) In vitro characterization of bicuspid aortic valve hemodynamics using particle image velocimetry. Ann Biomed Eng 40(8):1760–1775

    Google Scholar 

  • Saikrishnan N, Mirabella L, Yoganathan AP (2015) Bicuspid aortic valves are associated with increased wall and turbulence shear stress levels compared to trileaflet aortic valves. Biomech Model Mechanobiol 14(3):577–588

    Google Scholar 

  • Sider KL, Blaser MC, Simmons CA (2011) Animal models of calcific aortic valve disease. Int J Inflamm 2011:364310–364310

    Google Scholar 

  • Singh A, Greenwood JP, Berry C, Dawson DK, Hogrefe K, Kelly DJ, Dhakshinamurthy V, Lang CC, Khoo JP, Sprigings D (2017) Comparison of exercise testing and CMR measured myocardial perfusion reserve for predicting outcome in asymptomatic aortic stenosis: the PRognostic Importance of MIcrovascular Dysfunction in Aortic Stenosis (PRIMID AS) Study. Eur Heart J 38(16):1222–1229

    Google Scholar 

  • Spitzer E, Van Mieghem NM, Pibarot P, Hahn RT, Kodali S, Maurer MS, Nazif TM, Rodés-Cabau J, Paradis JM, Kappetein AP, Ben-Yehuda O, van Es GA, Kallel F, Anderson WN, Tijssen J, Leon MB (2016) Rationale and design of the transcatheter aortic valve replacement to UNload the Left ventricle in patients with ADvanced heart failure (TAVR UNLOAD) trial. Am Heart J 182:80–88

    Google Scholar 

  • Stalder AF, Frydrychowicz A, Russe MF, Korvink JG, Hennig J, Li K, Markl M (2011) Assessment of flow instabilities in the healthy aorta using flow-sensitive MRI. J Magn Reson Imaging 33(4):839–846

    Google Scholar 

  • Stein PD, Sabbah HN (1976) Turbulent blood flow in the ascending aorta of humans with normal and diseased aortic valves. Circ Res 39(1):58–65

    Google Scholar 

  • Sun L, Rajamannan NM, Sucosky P (2011) Design and validation of a novel bioreactor to subject aortic valve leaflets to side-specific shear stress. Ann Biomed Eng 39(8):2174–2185

    Google Scholar 

  • Sun L, Rajamannan NM, Sucosky P (2013) Defining the role of fluid shear stress in the expression of early signaling markers for calcific aortic valve disease. PloS one 8(12):e84433

    Google Scholar 

  • Thubrikar M (2018) The aortic valve. Routledge, Abingdon

    Google Scholar 

  • Thubrikar MJ, Deck JD, Aouad J, Nolan SP (1983) Role of mechanical stress in calcification of aortic bioprosthetic valves. J Thorac Cardiovasc Surg 86(1):115–125

    Google Scholar 

  • Timmins LH, Molony DS, Eshtehardi P, McDaniel MC, Oshinski JN, Giddens DP, Samady H (2017) Oscillatory wall shear stress is a dominant flow characteristic affecting lesion progression patterns and plaque vulnerability in patients with coronary artery disease. J R Soc Interface 14(127):20160972

    Google Scholar 

  • Tkatchenko TV, Moreno-Rodriguez RA, Conway SJ, Molkentin JD, Markwald RR, Tkatchenko AV (2009) Lack of periostin leads to suppression of Notch1 signaling and calcific aortic valve disease. Physiol Genom 39(3):160–168

    Google Scholar 

  • Toninato R, Salmon J, Susin FM, Ducci A, Burriesci G (2016) Physiological vortices in the sinuses of Valsalva: an in vitro approach for bio-prosthetic valves. J Biomech 49(13):2635–2643

    Google Scholar 

  • Tseng H, Grande-Allen KJ (2011) Elastic fibers in the aortic valve spongiosa: a fresh perspective on its structure and role in overall tissue function. Acta Biomater 7(5):2101–2108

    Google Scholar 

  • Van Ooij P, Powell AL, Potters WV, Carr JC, Markl M, Barker AJ (2016) Reproducibility and interobserver variability of systolic blood flow velocity and 3D wall shear stress derived from 4D flow MRI in the healthy aorta. J Magn Reson Imaging 43(1):236–248

    Google Scholar 

  • van Ooij P, Markl M, Collins JD, Carr JC, Rigsby C, Bonow RO, Malaisrie SC, McCarthy PM, Fedak PW, Barker AJ (2017) Aortic valve stenosis alters expression of regional aortic wall shear stress: new insights from a 4-dimensional flow magnetic resonance imaging study of 571 subjects. J Am Heart Assoc 6(9):e005959

    Google Scholar 

  • Verma S, Siu SC (2014) Aortic dilatation in patients with bicuspid aortic valve. N Engl J Med 370:1920–1929

    Google Scholar 

  • Wallby L, Janerot-Sjöberg B, Steffensen T, Broqvist M (2002) T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves. Heart 88(4):348–351

    Google Scholar 

  • Wang W, Vootukuri S, Meyer A, Ahamed J, Coller BS (2014) Association between shear stress and platelet-derived transforming growth factor-β1 release and activation in animal models of aortic valve stenosis. Arterioscler Thromb Vasc Biol 34(9):1924–1932

    Google Scholar 

  • Ward C (2000) Clinical significance of the bicuspid aortic valve. Heart 83(1):81–85

    Google Scholar 

  • Weinberg EJ, Mofrad MRK (2007) Transient, three-dimensional, multiscale simulations of the human aortic valve. Cardiovasc Eng 7(4):140–155

    Google Scholar 

  • Weinberg EJ, Kaazempur Mofrad MR (2008) A multiscale computational comparison of the bicuspid and tricuspid aortic valves in relation to calcific aortic stenosis. J Biomech 41(16):3482–3487

    Google Scholar 

  • Weinberg EJ, Schoen FJ, Mofrad MR (2009) A computational model of aging and calcification in the aortic heart valve. PLoS One 4(6):e5960

    Google Scholar 

  • Weinberg EJ, Mack PJ, Schoen FJ, Garcia-Cardena G, Kaazempur Mofrad MR (2010) Hemodynamic environments from opposing sides of human aortic valve leaflets evoke distinct endothelial phenotypes in vitro. Cardiovasc Eng 10(1):5–11

    Google Scholar 

  • Wu C, Daugherty A, Lu HS (2019) Updates on approaches for studying atherosclerosis. Arterioscler Thromb Vasc Biol 39(4):e108–e117

    Google Scholar 

  • Xiao X, Wu Z-C, Chou K-C (2011) A multi-label classifier for predicting the subcellular localization of gram-negative bacterial proteins with both single and multiple sites. PloS one 6(6):e20592

    Google Scholar 

  • Yap CH, Saikrishnan N, Tamilselvan G, Vasilyev N, Yoganathan AP (2012a) The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface. Am J Physiol Heart Circ Physiol 303(6):H721–H731

    Google Scholar 

  • Yap CH, Saikrishnan N, Tamilselvan G, Yoganathan AP (2012b) Experimental measurement of dynamic fluid shear stress on the aortic surface of the aortic valve leaflet. Biomech Model Mechanobiol 11(1):171–182

    Google Scholar 

  • Yap CH, Saikrishnan N, Yoganathan AP (2012c) Experimental measurement of dynamic fluid shear stress on the ventricular surface of the aortic valve leaflet. Biomech Model Mechanobiol 11(1):231–244

    Google Scholar 

  • Yoganathan AP, He Z, Casey Jones S (2004) Fluid mechanics of heart valves. Annu Rev Biomed Eng 6(1):331–362

    Google Scholar 

  • Youssefi P, Gomez A, He T, Anderson L, Bunce N, Sharma R, Figueroa CA, Jahangiri M (2017) Patient-specific computational fluid dynamics—assessment of aortic hemodynamics in a spectrum of aortic valve pathologies. J Thorac Cardiovasc Surg 153(1):8-20. e23

    Google Scholar 

  • Yutzey KE, Demer LL, Body SC, Huggins GS, Towler DA, Giachelli CM, Hofmann-Bowman MA, Mortlock DP, Rogers MB, Sadeghi MM (2014) Calcific aortic valve disease: a consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease. Arterioscler Thromb Vasc Biol 34(11):2387–2393

    Google Scholar 

  • Zhang R, Zhang Y (2020) Experimental analysis of pulsatile flow characteristics in prosthetic aortic valve models with stenosis. Med Eng Phys 79:10–18

    Google Scholar 

  • Zhong A, Simmons CA (2016) Heart valve mechanobiology in development and disease. In: Molecular and cellular mechanobiology, Springer, New York, pp 255–276

Download references

Acknowledgements

Dr. Hatoum reports having filed a patent application on computational predictive modeling of thrombosis in heart valves and on a Novel Implantable Vascular Shunt with Real-Time Precise Flow Control.

Funding

This research received no external funding.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hoda Hatoum.

Ethics declarations

Conflict of interest

No other conflict is reported.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vogl, B.J., Niemi, N.R., Griffiths, L.G. et al. Impact of calcific aortic valve disease on valve mechanics. Biomech Model Mechanobiol 21, 55–77 (2022). https://doi.org/10.1007/s10237-021-01527-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-021-01527-4

Keywords

Navigation