Ghent University Faculty of Engineering Department of Civil Engineering Department of Flow, Heat and Combustion Mechanics Experimental and numerical modeling of heart valve dynamics Experimentele en numerieke modellering van de hartklepdynamica ir. Kris Dumont Supervisors: Prof. Dr. Ir. Pascal Verdonck Prof. Dr. Ir. Jan Vierendeels Dissertation submitted to obtain the degree of Doctor in de Toegepaste Wetenschappen Academic Year 2004-2005 ©Kris Dumont, 2004. Experimental and numerical modeling of heart valve dynamics Experimentele en numerieke modellering van de hartklepdynamica The cover is designed by b-ART (Bart Dumont). Supervisors: Prof. Dr. Ir. Pascal Verdonck Prof. Dr. Ir. Jan Vierendeels Hydraulics Laboratory Department of Flow, Cardiovascular Research Group Heat and Combustion Mechanics IBiTech Faculty of Applied Sciences Institute Biomedical Technology Ghent University Civil Engineering Department Sint-Pietersnieuwstraat 41 Faculty of Applied Sciences B-9000 Gent, Belgium UGent, Ghent University Sint-Pietersnieuwstraat 41 B-9000 Gent, Belgium Exam Commission Prof. R. Verhoeven (president, Faculty of Engineering, UGent) Prof. P. Segers (secretary, Faculty of Engineering, UGent) Prof. W. Flameng (Faculty of Medicine and Health Sciences, KULeuven) Prof. R. Perrault (Lab. of Aerodynamic Studies, Universite´ de Poitiers) Prof. A. Redaelli (Dept. of Bioengieering, Politecnico di Milano) Prof. G. Van Nooten (Faculty of Medicine and Health Sciences, UGent) Prof. F. van de Vosse (Dep. of Biomedical Engineering, TUEindhoven) Prof. W. Van Paepegem (Faculty of Engineering, UGent) Prof. P. Verdonck (Faculty of Engineering, UGent) Prof. J. Vierendeels (Faculty of Engineering, UGent) This research was funded by the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-01775). Soon I’ll have the courage To leave my thoughts behind I’ll give back all the knowledge And keep the wisdom precious in my mind Massive Attack (Three) Acknowledgements Since 2000, it has been my privilege to be part of the Hydraulics Lab com- munity, physically rooted at the nice city of Ghent in Belgium. Although I’ve spent most of the past four years behind a computer doing stuff with heart valves, it is tough for most people to imagine how on earth it is possible to work for more than four years on these small heart valves. In following my own path toward completion of this PhD, I have learned not only about “How Heart Valves Work”, but I have learned many lessons; lessons about friend- ship, about football and victory, about science and innovation of technology, about people and their own culture, and many more. All these lessons made me more mature and they brought me to were I am right now. The last les- son for the completion of this PhD is the writing of a book. The writing of a dissertation can be a lonely and isolating experience, yet it is obviously not possible without the personal and practical support of numerous people. I thank my supervisors, Professor Pascal Verdonck and Professor Jan Vieren- deels for many insightful conversations during the development of the ideas in this thesis. I would like to thank Pascal Verdonck for my journey into Heart Valve Dynamics, for his wisdom, friendship, understanding, and for teaching me how to be a ‘successful’ researcher. I am particularly grateful to Jan Vierendeels for his thoughtful and creative comments on the complex topic of ‘Computational Fluid Dynamics’. I am appreciative and thankful for the support of my dissertation chair, Professor Ronny Verhoeven, and the mem- bers of my committee. Professor Patrick Segers raised broad conceptual questions and encouraged me to put more of my own commentary into the dissertation. I am grateful for having had two outstanding experts Professor Guido Van Nooten and Professor Frans van de Vosse as reviewers for my dissertation. I sincerely appreciate the efforts of all who contributed to this work in one way or another: Patke Kishor, Kevin Petersen, Marco Stijnen, Jessa Yperman, Bart Meuris, Willem Flameng. ix Acknowledgements I would also like to thank more than a dozen colleagues: Stefaan (De Mey), Peter, Stijn, Koen, Fadi, Sunny, Ilse, Tom, Guy, Seba, Lieve, Masanori, Dirk, Stefaan (Bliki), Martin, Marcel, Manuella, Jurgen, Ivo, who provided a source of knowledge, a nice drink or snack during coffee break, a ‘listening ear’, ... or whatever. I am fortunate to have colleagues who were willing to share their time and expertise to improve my scientific work and writing. Their friendship and professional collaboration meant a great deal to me. Stijn and Sunny dissected the stylistic and grammatical shortcomings of my ear- lier drafts. To the best of my capabilities, I followed their advice. Their wis- dom and compliments are greatly appreciated. Not least, perhaps, I should thank my girlfriend, Frauke, for her patience and forbearance whilst I have spent hundreds of hours working on it! Futher- more, thank you ‘Ma’ and ‘Pa’ for patiently tolerating the rollercoaster ride of moods that accompanied my struggles writing this book. You were there since I was born to share the excitement of my stories, and this sustained me through the highs and the lows. To my dear little sister Tinneke, I want to say ‘thanx’ for the cooking of the last months and just for spending time with me. I hope you can find your “knight in shiny armour” in the near future. Joren, Anke, Bart and Heidi thanks for the holidays, the drinks, the running- and-biking, the design of the frontpage by b-ART and many more. Special thanks to Paul and Nicole the dear parents of Frauke for providing not only the meat, but more important a lovely daughter. Good luck to their son, Niels alias ‘the Hobbit’ with his studies. Because of the large families we have it is impossible to mention everybody, but still: ‘Thank You!’ A special moment of silence to my grand parents who passed away, Vake and Meme. I would like you to know that I love you! To Moeke and Pepe I would like to say: ‘Stay with us for many more years!’. I would like to thank Niek and Marten who have encouraged me during several mountainbike trips. Also, my long standing friends - Simon and Ka(trien& Ber)nard. The conversations in the pubs, the beer and wine, the nice dinners, the parties, the fishing afternoons, the sporting, the biking, ... were very helpful to forget the struggle of the PhD; thanx to the friends of x my parents, the football team ‘Campus’, Koenie, alias ‘the dancer’, Daan and Veerle, Kim and Andy, Marlies and Wim, Nele and Pedro, the “Gidsen”-girls, Glen, Jimmy and Ingrid, Fatima and Jo, Alain and Anne-Greet, Frederik and Caroline and many more. Special thanks to Evy and Wim for their warm wel- come upon my arrival in Manhattan, New York. Muchas gracias Isabeeltje y Tine, por todo el tiempo y la fiesta en los lecciones espanoles.˜ Though some of these people may not directly be involved in my thesis writing, the words of all the above and of everybody I forgot to mention were really important for keeping me to work hard and never give up my thesis. The power of language is really amazing, and it can make people from weak to strong. Thanks for all the support!!! Kris Dumont Gent, December 2004 xi Contents Acknowledgements ix Notations, Symbols and Abbreviations xxvii Preface ........................................... 1 A Introduction 5 I Anatomy and physiology of heart valves 7 I.1 The human heart and circulation .......................... 7 I.2 The cardiac cycle .................................. 9 I.3 How valves function ................................. 10 I.3.1 Atrioventricular valves .......................... 10 I.3.2 Semilunar valves ............................. 10 I.4 Histology of heart valves .............................. 12 I.4.1 Valvular interstitial cells .......................... 12 I.4.2 Valvular endothelial cells ......................... 13 I.4.3 Heart valve extracellular matrix ...................... 13 I.5 Mechanical properties of the aortic valve leaflets . 14 I.6 Rheology of blood .................................. 15 II Heart valve disease and treatment 19 II.1 Causes of heart valve disease ............................ 19 II.2 Diagnosis ...................................... 20 II.3 Types of heart valve disease ............................. 22 II.3.1 Mitral valve prolapse ........................... 23 II.3.2 Mitral regurgitation ............................ 25 II.3.3 Mitral stenosis ............................... 25 II.3.4 Aortic regurgitation ............................ 26 II.3.5 Aortic stenosis ............................... 28 II.3.6 Tricuspid and pulmonary stenosis and regurgitation . 28 II.4 Treatment ...................................... 29 II.4.1 Drugs ................................... 29 xiii Contents II.4.2 Balloon valvuloplasty ........................... 29 II.4.3 Surgical repair ............................... 30 II.4.4 Valve replacement surgery ........................ 30 II.5 Recent developments: progress towards a tissue engineered heart valve . 36 II.5.1 Tissue engineering approach to heart valve replacement . 36 II.5.2 Bioreactor technologies .......................... 37 II.5.3 Current progress towards a Tissue Engineered Heart Valve . 39 III Haemodynamic assessment of heart valves 43 III.1 Parameters derived from flow and pressure data ................... 43 III.1.1 Cardiac output ............................... 43 III.1.2 Pressure gradient ............................. 44 III.1.3 Effective orifice area and performance index . 46 III.1.4 Regurgitation