Contents



Chapter 6 **Proteomics and Metabolomics in Aortic Stenosis: Studying Healthy Valves for a Better Understanding of the Disease 151** L. Mourino-Alvarez, C.M. Laborde and M.G. Barderas


Chapter 16 **Indications for Transcatheter Aortic Valve Implantation 483**

Chapter 17 **Aortic Valve Replacement for Calcified Aortic Valves 499**

Christoph A. Nienaber and Hüseyin Ince

Chapter 18 **Congenital Aortic Stenosis in Children 517** Hirofumi Saiki and Hideaki Senzaki

Kazumasa Orihashi

Ibrahim Akin, Stephan Kische, Henrik Schneider, Tim C. Rehders,

Contents **VII**


Chapter 7 **Genetics of Bicuspid Aortic Valve and Calcific Aortic**

**Section 4 New Strategies in Heart Valve Tissue Engineering and**

Chapter 8 **The Immune Response in In Situ Tissue Engineering of Aortic**

Chapter 9 **Cutting-Edge Regenerative Medicine Technologies for the Treatment of Heart Valve Calcification 247**

S. L. M. van Loon, A. I. P. M. Smits, A. Driessen-Mol, F. P. T. Baaijens

George Tokmaji, Berto J. Bouma, Dave R. Koolbergen and Bas A.J.M.

Stamenko Šušak, Lazar Velicki, Dušan Popović and Ivana Burazor

Fahrettin Oz, Fatih Tufan, Ahmet Ekmekci, Omer A. Sayın and

Omer Leal, Juan Bustamante, Sergio Cánovas and Ángel G. Pinto

Chapter 14 **Stentless Bioprostheses for Aortic Valve Replacement in Calcific**

Chapter 15 **New Therapeutic Approaches to Conventional Surgery for Aortic Stenosis in High-Risk Patients 451**

**Regenerative Medicine 205**

**Valve Disease 173** Robert B. Hinton

**VI** Contents

**Heart Valves 207**

and C. V. C. Bouten

**Section 5 Bicuspid Aortic Valve 303**

Chapter 10 **Bicuspid Aortic Valve 305**

Chapter 11 **The Bicuspid Aortic Valve 335** Mehmet Demir

**Mechanical) 361**

Huseyin Oflaz

Kaan Kirali

**Aortic Stenosis 411**

**Section 6 Current Treatment Approaches 359**

Chapter 12 **Surgical Valve Replacement (Bioprosthetic vs.**

Chapter 13 **Current Treatment Options in Aortic Stenosis 379**

de Mol

Laura Iop and Gino Gerosa

Preface

near future.

Valvular heart diseases represent an underappreciated yet serious and growing problem. Due to population aging, calcific aortic valve disease (CAVD) has become the most common heart valve disease in developed and rapidly developing regions of the world, affecting ap‐ proximately 25% of adults over 65 years of age. No therapies exist to slow this disease pro‐ gression, and surgical valve replacement is the only effective treatment. More than 275,000 aortic valve replacements are performed annually worldwide, and this number is expected to triple by 2050. Although rheumatic heart disease continues to be an important problem in developing countries, its prevalence has generally declined. This book will address CAVD as a common heart valve disease, focusing predominantly on the underlying mechanisms and current treatment approaches. We hope that this book will enable readers to grasp the current knowledge and focus on the possibility of preventing disease progression in the

The book is divided into six sections and comprised of 18 chapters written by well-recog‐ nized investigators from United States, Europe, and Asia. Section I focuses on the biology and function of the normal aortic valve. Chapter 1 is written by a research group lead by Dr. K. Jane Grande-Allen, a renowned investigator in the field of cardiac valve extracellular ma‐ trix and valve biology. It describes the role of major and minor matrices in normal valves, focusing on extracellular matrix function and biomechanical properties. Chapter 2, written by Prof. Tilea Ioan, deals with the anatomy and function of normal aortic valve components. Section II provides current insight into the mechanisms of CAVD. It begins with Chapter 3, written by Prof. Katherine Yutzey, a prominent scholar in valve developmental biology, who provides an overview of signaling pathways involved in valve development and their reactivation during CAVD progression. This chapter also describes osteogenic-related mo‐ lecular pathways involved in CAVD, and provides an outlook on developing therapeutics to treat CAVD. The next two chapters (Chapter 4, written by Dr. Erik Fung, and Chapter 5, written by Dr. Claudia Goettsch) offer evolving insights into the mechanisms of CAVD, in‐ cluding NOTCH signaling and microRNA dysregulation. Topics covered in Section III in‐ clude proteomics and metabolomics in Chapter 6, written by Dr. Maria Barderas; and genetics in Chapter 7, written by Dr. Robert Hinton. Both chapters represent innovative technology platforms recently developed to identify DNA, RNA, proteins, and peptides in different biological compartments, which could serve as biomarkers for various diseases. Section IV reviews advances in the field of heart valve tissue engineering and is comprised of two chapters written by leaders in the field (Chapter 8, written by Prof. Carlijn Bouten, and Chapter 9, written by Prof. Gino Gerosa). New cutting-edge approaches, including heart valve tissue engineering and tissue-guided regeneration, have been proposed to over‐ come the limitations of current valve substitutes. These chapters describe the foreign body
