The

Aortic Valve

Author
Mano Thubrikar
Associate Professor
Department of Surgery
University of Virginia Health Sciences Center
Charlottesville, Virginia

informa
healthcare
New York London
First published in 1990 by CRC Press, Inc.

This edition published in 2011 by Informa Healthcare, Telephone House, 69-77 Paul Street, London EC2A
4LQ, UK.

Simultaneously published in the USA by Informa Healthcare, 52 Vanderbilt Avenue, 7th Floor, New York,
NY 10017, USA.

Informa Healthcare is a trading division of Informa UK Ltd. Registered Office: 37-41 Mortimer Street,
London W1T 3JH, UK. Registered in England and Wales number 1072954.

©2011 Informa Healthcare, except as otherwise indicated

No claim to original U.S. Government works

Reprinted material is quoted with permission. Although every effort has been made to ensure that all
owners of copyright material have been acknowledged in this publication, we would be glad to
acknowledge in subsequent reprints or editions any omissions brought to our attention.

All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or
transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise,
unless with the prior written permission of the publisher or in accordance with the provisions of the
Copyright, Designs and Patents Act 1988 or under the terms of any licence permitting limited copying
issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London W1P 0LP, UK, or the
Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA (h ttp ://w w w .
[Link]/ or telephone 978-750-8400).

Product or corporate names may be trademarks or registered trademarks, and are used only for
identification and explanation without intent to infringe.

This book contains information from reputable sources and although reasonable efforts have been made
to publish accurate information, the publisher makes no warranties (either express or implied) as to the
accuracy or fitness for a particular purpose of the information or advice contained herein. The publisher
wishes to make it clear that any views or opinions expressed in this book by individual authors or
contributors are their personal views and opinions and do not necessarily reflect the views/opinions of
the publisher. Any information or guidance contained in this book is intended for use solely by medical
professionals strictly as a supplement to the medical professional's own judgement, knowledge of the
patient's medical history, relevant manufacturer's instructions and the appropriate best practice
guidelines. Because of the rapid advances in medical science, any information or advice on dosages,
procedures, or diagnoses should be independently verified. This book does not indicate whether a
particular treatment is appropriate or suitable for a particular individual. Ultimately it is the sole
responsibility of the medical professional to make his or her own professional judgements, so as
appropriately to advise and treat patients. Save for death or personal injury caused by the publisher's
negligence and to the fullest extent otherwise permitted by law, neither the publisher nor any person
engaged or employed by the publisher shall be responsible or liable for any loss, injury or damage caused
to any person or property arising in any way from the use of this book.

A CIP record for this book is available from the British Library.

Library of Congress Cataloging-in-Publication Data available on application

ISBN-13: 9780849347719

Orders may be sent to: Informa Healthcare, Sheepen Place, Colchester, Essex CO3 3LP, UK
Telephone: +44 (0)20 7017 5540
Email: CSDhealthcarebooks@[Link]
Website: [Link]

For corporate sales please contact: CorporateBooksIHC@[Link]

For foreign rights please contact: RightsIHC@[Link]
For reprint permissions please contact: PermissionsIHC@[Link]
 PREFACE
The aortic valve is a fascinating structure. It opens and closes about 103,000 times a day. Its
dynamics are quite demanding because they are traumatic. The aortic valve sustains variable
pressure, undergoes complete reversal of curvature, and is subjected to a large amount of flexion
for billions of cycles and still survives. No man-made structure can boast this achievement. In
understanding this structure lies enhancement of our knowledge. A vivid picture of the aortic
valve can be created by simply imagining three flaps moving back and forth in a swing-and-
pause motion, constantly opening and closing the valve.
The book probes step-by-step into various aspects of this structure. The geometry is
considered and the principles of valve design are revealed. The tissue composition is described
as well as how the tissue is best suited for the valve function. The dynamic motion, which
describes the very function of the valve, is considered. The mechanism of valve opening and
changes in the leaflet shape are considered. The blood flow, for the control of which the valve
exists, is described. The mechanism of closure and how the flow governs the leaflet position is
described. The mechanical properties of the tissue and the stresses that develop in the
functioning valve are described. Throughout these descriptions a link is maintained between the
geometry, tissue, motion, flow, and mechanics.
The échocardiographie studies are described to relate the clinical findings with the experi­
mental observations. The mechanism of second heart sound production is described. The diseaes
of the valve are described and theories for valvular stenosis explained. Finally, mechanical and
bioprosthetic valves are described. A broad perspective is developed in dealing with normal,
pathologic, and bioprosthetic valves by exploring the commonality between them through
comparisons of their design, dynamics, properties, function, and outcome. Interrelationships
between several different aspects of the valve are constantly pointed out so as to develop a
complete cohesive understanding of how the valve works.
At the present time there is a compelling reason to bring together the knowledge of the aortic
valve. Most bioprosthetic valves implanted in humans fail in 8 to 16 years and, therefore, the
search for a better valve continues. The information contained in this book will help in
developing a better bioprosthesis. Theories of calcific stenosis in the natural aortic and
bioprosthetic valves can be understood with the help of this book. The book enhances our ability
to interpret angiographic and échocardiographie images of the aortic valve. Owing to technical
developments during the last 15 years, new fundamental information was discovered about the
aortic valve. This book brings newly discovered information together and presents it in such a
way that the subject can be understood comprehensively. Each chapter in the book was reviewed
by two or three outside and internal experts in the field, which has imparted an unusually high
quality to the text. The book is also an example of how interdisciplinary work can achieve results
that are otherwise impossible to obtain.
The book will be useful to cardiovascular surgeons, cardiologists, and cardiac pathologists,
since it describes normal and abnormal geometries of the aortic valve, valvular pathology,
replacement valves, angiography, and ultrasonography. It will be useful to anatomists in relating
structure of the valve to function. It will be useful to manufacturers of mechanical and
bioprosthetic valves. The book will be useful to students in physiology and biomedical
engineering because it describes the principles of physiology and engineering and illustrates
their applications to the aortic valve. It brings medicine and engineering disciplines together
using the aortic valve as an example and therefore serves as a unique source of teaching and
interdisciplinary approaches. From this book both the medical and engineering students can
benefit by learning how to study the problems in medicine and how to discover scientific
explanations for them. With the help of the book many researchers will be able to expand their
research to include interdisciplinary approaches.
 THE AUTHOR

Mano Thubrikar, Ph.D., is Associate Professor in the Department of Surgery and Director
of Surgical Research at the University of Virginia Health Sciences Center at Charlottesville,
Virginia.
Dr. Thubrikar obtained his B.E. degree (first in the Order of Merit) in 1969 in Metallurgy and
Materials Science from Nagpur University, India. From New York University he obtained his
M.S. in 1971 in the same field and his Ph.D. in 1975 in Biomedical Engineering. He served as
a Research Instructor and as a Research Assistant Professor from 1975 to 1982 in the Department
of Surgery at the University of Virginia, where he also assumed his present position in 1982.
Dr. Thubrikar is a member of the American Association of University Professors, Alliance
of Engineering in Medicine and Biology Society, American Society of Artificial Internal
Organs, Biomedical Engineering Society, International Association for Cardiac Biological
Implants, and Council on Arteriosclerosis.
He has been the recipient of the Research Career Development Award (1980— 1985) from
the National Institutes of Health and the Certificate of Merit awarded by the New York Academy
of Medicine. He has been the recipient of research grants from the National Institutes of Health,
the Diabetes Research Center of the University of Virginia, and private industries.
He has published more than 68 papers and presented 29 lectures at national and international
meetings. He has been an invited speaker at several international symposiums. He has been a
consultant to private industries and has developed collaborative programs between universities.
His current research interests are in natural, pathologic, and bioprosthetic aortic valves and the
mechanism of atherosclerosis.
 ACKNOWLEDGMENTS

I am deeply indebted to Dr. Stanton P. Nolan who has contributed immensely to the work
presented here and whose support and encouragement were essential for the preparation of this
book.
I express my thanks to the following individuals for reviewing parts of the book: J. David
Deck, Ph.D. and Richard E. Clark, M.D. (Chapter 1); Victor J. Ferrans, M.D. (Chapter 2);
Stanton P. Nolan, M.D. and James L. Heckman, Ph.D. (Chapter 3); Anton A. van Steenhoven,
Ph.D. and Charles S. Peskin, Ph.D. (Chapter 4); Richard T. Eppink, Ph.D. and Phillip L. Gould,
Ph.D. (Chapter 5); Sanjiv Kaul, M.D. (Chapter 6); Louis G. Durand, M.D., Ph.D. (Chapter 7);
R. Scott Jones, M.D., Stanton P. Nolan, M.D., and Kuldeep Teja, M.D. (Chapter 8); and
Frederick J. Schoen, M.D. and Neil D. Broom, Ph.D. (Chapter 9). Their comments have
enhanced the quality of each chapter. I am thankful to Drs. Robert Harry, Paul Bosher, William
Piepgrass, James Skinner, Jaafar Aouad, Lynn Levitt, Mr. Anthony Broccoli, and Ms. Marjorie
Garmey for their contribution to the research headed by Dr. Nolan and myself, which makes up
a substantial part of this book. Thanks are due to Gail K. Schroeder, Norma Miller, Linda
Powley, and Carole Hoadley for their assistance in preparing the manuscript. Finally, thanks are
also due to my wife, Sudha Thubrikar, for her patience during the writing of the book.
 To my parents,
Jumdeoji and Varanasi Thubrikar
 TABLE OF CONTENTS

Chapter 1
Geometry of the Aortic Valve ....... ............................................................................................ 1
I. Introduction............................................................................................................................1
II. Heart and Heart V alves.... ........ 1
III. Valve A natom y...................... .2
A. Functional Importance of Valve A natom y................................................................6
IV. Dimensions of the V alve......................................................................................................8
V. Principles of Valve Design................................................................................................. 11
A. Construction of the Valve M odel............................................................................11
B. Valves of Various D esigns...................................................................................... 12
C. Performance Criteria......................................... 12
D. Geometric Relationships........................ 14
E. Process of Optimization................................... 15
F. The Design of the Natural Aortic V alve........................................ 16
G. The Effect of Dimensional Changes.............. 17
H. The Role of the Coapting Surface of the Leaflet................................................... 17
References............................................................................. 19

Chapter 2
Histology and Cytology of the Aortic Valve...................................................................... 21
I. Introduction........................................................ 21
II. General Features and Histology of the V a lv e..................................................................22
III. Electron Microscopy of the Valve ....................... 27
IV. Tissue R enew al................................................................ 33
References......................................... 36

Chapter 3
Dynamics of the Aortic Valve ...................................................................................................39
I. Introduction ......................................................................................................................... 39
II. Opening and Closing of the V alve................................................................ 39
A. The Valve O rifice.....................................................................................................39
III. The Leaflet Motion................... ....40
IV. Motion of Various Parts of the V alv e................................................... 45
A. Motion of the Commissures......................................... 46
B. The Mechanism of Opening of the Aortic V alv e............. ....48
C. Motion of the B a s e ...... .................................................................................. 54
D. Motion of the Aortic Annulus and Aortic Sinuses, and Change in
Leaflet Length........................................................................................................... 59
V. Design of the Valve In V ivo.............................................................................................. 61
VI. High-Speed Studies of the Leaflet M otion....................... 66
References................................................................................... 72

Chapter 4
Fluid Dynamics of the Aortic Valve .......................................... 75
I. Introduction.... .................................................................................................................... 75
II. Model I .................................................................................................................................75
A. Leaflet Position at Peak Systole in Steady F lo w ...................................................78
B. Deceleration Phase....... ...................................................................... 81
III. M o d e lli........................ 83
IV. Model I I I ............................................................................................................................. 90
V. Velocity Distribution.......................................................................................................... 90
VI. Blood Flow in the Ascending Aorta of Hum ans..............................................................92
References...................................................................................................................................... 94

Chapter 5
M echanical Stresses in the Aortic V alve.................................................................................97
I. Introduction......................................................................................................................... 97
II. Stress-Strain Properties of the Leaflet In V itro................................................................97
A. Uniaxial Stress-Strain Properties.............................................................................97
B. Stress-Strain Properties of the Leaflet in an Intact Closed V a lv e .................... 101
III. Stress-Strain Properties of the Leaflet In Vivo (Changes in the Length of
the L eaflet).........................................................................................................................101
A. Leaflet Length in the Circumferential Direction................................................ 101
B. Leaflet Length in the Radial Direction................................................................ 105
IV. Determination of Stresses in the Leaflet In Vitro.............................................. 108
A. Human Aortic Valve in the Closed Position.........................................................108
V. Determination of Stresses in the Leaflet In Vivo............................................................112
A. Canine Aortic Valve in a Functional S tate...........................................................113
VI. Stress Sharing between the Sinuses and the Leaflets.................................................... 119
A. Malformed Valves and Bioprostheses.................................................................. 123
References.................................................................................................................................... 126

Chapter 6
Echocardiography of the Aortic V a lv e ................................................................................. 129
I. Introduction........................................................................................................................129
II. M-Mode Echocardiography of the Aortic V alv e...........................................................130
III. Two-Dimensional Echocardiography of the Aortic Valve............................................132
IV. Echocardiography of Diseased Aortic V alves............................................................... 136
References.................................................................................................................................... 139

Chapter 7
Production of Aortic Valve S ound..........................................................................................141
I. Introduction........................................................................................................................141
II. Timing of the Second Heart Sound................................................................................. 141
III. Origin of the Second Heart S ound.................................................................................. 143
A. Frequency Content of the Second Heart Sound................................................... 148
B. Pathologic Conditions Affecting the Second Heart Sound................................. 149
IV. Theory of the Aortic Valve Vibration............................................................................. 150
References.................................................................................................................................... 156

Chapter 8
Diseases of the Aortic V alve.................................................................................................... 157
I. Introduction........................................................................................................................157
II. Aortic Stenosis.................................................................................................................. 157
III. Aortic Insufficiency...........................................................................................................157
IV. Congenital Bicuspid Aortic V a lv e.................................................................................. 158
V. Unicuspid and Quadricuspid V alves............................................................................... 160
VI. Variation in Size of the Three L eaflets...........................................................................161
VII. Theories of Isolated Aortic Stenosis............................................................................... 162
VIII. Age-Related Changes in the Leaflets.............................................................................. 164
IX. Patterns of Calcific Deposits............................................................................................167
References.................................................................................................................................... 173
Chapter 9
Replacement Cardiac Valves .................................................................................................. 175
I. Introduction....................................................................................................................... 175
II. Mechanical V alves............................................................................................................175
III. Bioprostheses.................................................................................................................... 178
A. Design and Construction.........................................................................................179
B. Performance In V ivo............................................................................................... 181
C. Hemodynamic Evaluation and D urability............................................................188
D. Mechanical Factors Related to Valve L ife ...........................................................191
IV. Homografts........................................................................................................................ 203
References....................................................................................................................................206

Appendix I ...................................................................................................................................209

Appendix I I ..................................................................................................................................211

Index ............................................................................................................................................ 213

 Chapter 1

GEOMETRY OF THE AORTIC VALVE

I. INTRODUCTION

The aortic valve consists of three membranous leaflets and aortic sinuses. The valve is located
between the left ventricle and the aorta and its function is to allow the blood to flow in one
direction, from the ventricle to the aorta. The valve separates the ventricle from the aorta. The
geometry of the valve will be described in four sections: (1) heart and heart valves, (2) valve
anatomy, (3) dimensions of the valve, and (4) principles of valve design.

II. HEART AND HEART VALVES

The heart has four chambers (right atrium, right ventricle, left atrium, and left ventricle) and
four valves (tricuspid, pulmonary, mitral, and aortic valves) (Figure 1). The tricuspid valve is
located between the right atrium and the right ventricle, the pulmonary valve between the right
ventricle and the pulmonary artery, the mitral valve between the left atrium and the left ventricle,
and the aortic valve between the left ventricle and the aorta. The tricuspid and mitral valves are
called atrioventricular valves since they are between the atrium and the ventricle, and the
pulmonary and aortic valves are called arterioventricular valves since they are between the
artery and the ventricle. The aortic and pulmonary valves are also called semilunar valves
because their leaflets have the shape of a half moon. Atrioventricular valves are attached to the
heart muscle (myocardium) by means of papillary muscles and fibrous cords and are considered
to be active structures responding to myocardial contractions. Semilunar valves, on the other
hand, do not have direct attachment of the mobile part of the leaflet to the myocardium, and
therefore have been considered in the past to function passively in response to blood flow. It will
be shown that parts of the aortic valve are active.
All of the valves permit blood flow in one direction (Figure 1). Oxygen-depleted blood
returns from the body via venae cavae to the right atrium and through the tricuspid valve to the
right ventricle. It then goes through the pulmonary valve to the pulmonary artery, and to the
lungs. Oxygenated blood from the lungs returns via pulmonary veins to the left atrium and
through the mitral valve to the left ventricle. It then goes through the aortic valve to the aorta,
and finally to the whole body. The flow of blood is achieved by the pumping action of the heart.
During ventricular ejection, aortic and pulmonary valves remain open and mitral and tricuspid
valves remain closed, and during ventricular filling, aortic and pulmonary valves remain closed
and mitral and tricuspid valves remain open.
The aortic valve opens to allow blood to flow into the aorta, and closes to prevent backflow
into the ventricle. The valve opens and closes approximately 103,000 times each day and
approximately 3.7 billion times in its life span. This opening and closing of the aortic valve is
achieved by the movement of its three leaflets. To create a mental picture of the aortic valve in
action, imagine three leaflets opening and closing, like the shutter of a camera, with each
heartbeat. Although the aortic valve performs the same task as man-made valves, it is unique in
its accomplishments since no man-made valve, to date, can serve that function with the same
efficiency and durability. This fact becomes consequential when a diseased aortic valve has to
be replaced with a prosthetic device which must now perform the same task (see Chapter 9).
Although diseases of any of the heart valves can compromise health, diseases of the aortic
or the mitral valve result in more dire consequences, which therefore puts greater importance
on the function of these two valves.
 The Aortic Valve

FIGURE 1. Drawing of the heart showing its chambers and valves. RA —

right atrium, RV — right ventricle, LA — left atrium, LV — left ventricle,
T — tricuspid valve, P — pulmonary valve, M — mitral valve, A — aortic
valve, PA — pulmonary artery, AO — aorta. Arrows indicate the path of
blood flow.

III. VALVE ANATOMY

The aortic valve consists of three leaflets and three sinuses (Figures 2 and 3). The leaflets are
the most mobile parts of the valve and the sinuses are cavities behind the leaflets. At the lower
margin, the sinuses become continuous with the left ventricle, and at the upper margin they
become part of the ascending aorta. The sinuses represent dilations of the base of the aorta.
When the aortic root is excised and fixed at diastolic pressure with the leaflets closed, its
outside wall is seen to be formed by three aortic sinuses ballooning outward in the shape of
ellipsoids (Figure 31). Next to the ventricle, the proximal ends of these ellipsoidal sinuses are
separated from each other by three wedge-shaped trigonal regions in the wall (Figure 3II).
Looking inside the root from its aortic opening, one can see the sinuses as divergent pockets
bulging laterally above the closed leaflets. Apertures of the right and left coronary arteries are
present in two of the sinuses; the third is a blind sac. Accordingly, the sinuses are named right
coronary sinus, left coronary sinus, and noncoronary (or posterior) sinus (Figure 3II).
From the aortic view, the closed leaflets appear to be composed of two parts. One part
separates the ventricle from the aorta, bearing the load of aortic pressure (Figure 3IV). This is
the only part of the leaflet visible from the ventricular perspective (Figure 2-top). The second
part of each leaflet is that which coapts against the other two leaflets and apparently bears no
FIGURE 2. Top: The closed aortic valve viewed from below. The three coapting leaflets of the valve, the aorta above,
and the ventricular myocardium along with aorto-ventricular membrane below are seen. The membrane becomes
continuous with the anterior leaflet of the mitral valve. Only the load-bearing portion of the leaflet is visible. Left: The
aortic view of the closed valve. Free edges of the leaflets meet at a 120° angle. Coapting surfaces, passing through the
free edges, are perpendicular to the plane of the figure. The noduli are in the center and the site of leaflet attachment
at their nadir is indicated by arrows. Right: A direct view of a single leaflet. The nodule of Arantius at the center of
the free edge appears unusually prominent in this leaflet. The inferior margin of the lunules which is also the line of
leaflet coaptation marks a separation between the coaptation surface above and the load-bearing surface below. The
line of leaflet attachment to the aortic wall has a crescentic shape. (From Me Alpine, W. A., Heart and Coronary
Arteries, Springer-Verlag, New York, 1975. With permission.)

load. This part is called the coaptation surface or redundant surface. It will be shown that a
portion of the coaptation surface does bear a load and therefore should not be considered
redundant. The only free boundary of the leaflet, which is also the distal boundary of the
coaptation surface and which is visible from the aorta, is called the free edge of the leaflet (Figure
2 and Figure 3IV).
Excision of leaflets and sinuses can help to clarify the interrelationships of these parts. If the
leaflets are cut away from the wall it can be seen that the aortic surface of each leaflet is inserted
along a crescentic line that follows the proximal border of its companion sinus (Figure 3II, III).
 The Aortic Valve

Ao

III

IV

FIGURE 3. I: Aortic valve in the closed position. One leaflet and the corresponding sinus have been removed.
Coronary arteries are not shown. C — commissure; F — free edge; L — lunula; N — node of Arantius; S — sinus wall,
T — top of a sinus cavity. (From Sauren, A., The Mechanical Behavior o f the Aortic Valve, Thesis. With permission.)
II: Schematic presentation of the aortic valve opened with a longitudinal incision. L, R, and N represent left, right, and
noncoronary (posterior) sinus, respectively. The dotted line shows scallop-shaped upper borders of the sinuses. The
ostia of the coronary arteries are shown in R and L sinuses. (From Me Alpine, W. A., Heart and Coronary Arteries,
Springer-Verlag, New York, 1975. With permission.) Ill: Configuration of the line of leaflet attachment to the aortic
wall. IV: Drawing of a single leaflet,. FE — free edge, C — line of coaptation, A — line of attachment, R — redundant
(coaptation) surface, L — load-bearing surface. Circumferential (CD) and radial (RD) directions of the leaflet are
shown.

The insertion of the ventricular surface follows a different line, separated from the aortic surface
by a relatively thick basal region of the leaflet. The leaflet commissures are formed by the mural
regions where two leaflets insert side by side along parallel lines. The sinuses merge with each
other at the commissures and continue across the sinus rim distally into the aorta (Figure 31).
Another cut, made through the wall along the curved margins of the sinuses, leaves three trigonal
regions at the proximal border of the aortic root (Figure 3II, III). This scalloped border appears
as a three-pointed coronet. This coronet-shaped structure has been classically, but somewhat
misleadingly, called the “fibrous ring”. In fact, the fibrous elements of the root do not exist as
a planar ring but form the scalloped border of a coronet. The upper borders of the sinuses also
do not form a circular ring in a single plane. Instead they are scalloped (Figure 31, II). Distally,
where the leaflets come together, their line of attachment runs parallel through a certain distance.
This distance will be referred to as commissural height, a term not generally found in the
literature.
The shapes of the sinuses and the leaflets as well as their interrelationships can be better
appreciated from root casts (Figure 4). From the ventricular perspective such casts show that the
three sinuses and the leaflets balloon outward from the aortic stem and form intersecting arcs
FIGURE 4. (A) Silicone rubber cast of the aortic root. Three sinuses and the leaflets appear to
balloon outward from the aorta. (From Karara, H. M., Report on a study sponsored by NASA
— Lyndon B. Johnson Space Center, Houston, TX, Contract No. NAS-9-12459. With
permission.) (B) Longitudinal section through the cast dividing one sinus and leaflet in half. The
sinus is curved in the longitudinal direction and the leaflet is flat in the radial direction (compare
with Figure 3A). (From Mercer, J. L. et al., J. Thorac. Cardiovasc. Res., 65 (4), 511,1973. With
permission.) (C) Silicone rubber cast of the aortic root viewed from the ventricular aspect.
Sinuses are curved in the circumferential direction. The load-bearing surface of one leaflet is
shaded to show the configuration of the line of leaflet attachment to the sinus wall. (D) Drawing
of the aortic valve. The leaflet is curved in the circumferential direction but flat in the radial
direction. (C, D: From Swanson, W. M. and Clark, R. E., Circ. Res., 35, 871, 1974. By
permission of the American Heart Association, Inc.) (E) Drawing of the aortic valve showing
the side view of one leaflet. The sinus has a doubly curved surface. The leaflet has a singly
curved surface. The line of leaflet attachment in the load-bearing portion lies in a plane.
 The Aortic Valve

(B)

■c3 O'
FIGURE 5. Top: Drawing to show planes A and B where the root cast is
sectioned. A: Section along plane A. Sinuses (L, R, N) are curved circum­
ferentially. Coronary arteries arising from L and R sinuses are shown. B:
Oblique section along plane B. The leaflet (L) and sinus (S) together have a
circular boundary.

(Figure 4A, C, D). The sinuses and leaflets may differ in size, making the root slightly
asymmetrical. If one follows the scalloped border of the coronet, the cast shows sacculations in
the aortic surface of each leaflet where it is attached basally. The rounded prominences
representing sacculations are indented from ridges and irregularities on the leaflet surfaces. The
surface of each leaflet is curved in only one plane, not two as is commonly shown (Figure 4B,
D, E). The leaflet can be regarded as a segment of a cylinder. The load-bearing surface is flat
in the radial plane, and the surface shows a bend into the coapting surface which is also flat. The
coapting surface of the leaflet can be considered to be made of two flat regions that meet in the
center of the valve at an angle of approximately 120° to produce a three leaflet symmetry
(Figures 2,31, IV). The bend, which represents a line of separation between the load-bearing and
coapting surfaces of the leaflet, is called the line of leaflet coaptation (Figure 31V). The line also
represents the proximal boundary of contact between adjacent leaflets. It has been reported^ that
the line of leaflet attachment in the load-bearing part of the leaflet lies in a plane (Figure 4E).
The contours of sinuses and leaflets are more clearly shown in slices from casts of the aortic
root (Figure 5). A section of a cast cut transversely through the middle of the sinuses shows that
in this plane each sinus forms the arc of a circle (Figure 5A). If the cast is cut vertically through
the middle of the sinus, the sinus appears to have the curvature of an ellipse. The vertical cut also
bisects the adjacent leaflet surface in its radial plane and clearly demonstrates that the pressure­
bearing surface is indeed flat in this plane (Figure 4B).
When serial sections of the cast are cut obliquely in the direction perpendicular to the axis
of the leaflet surface (Figure 5-top, B), i.e., in the circumferential plane of the leaflet, they
demonstrate that the leaflet surface forms a circular arc. Indeed, a circumferential cut through
the middle of the leaflet into the sinus wall shows that the luminal surface of leaflet and sinus
together appears as a full circle. The overall shape of the sinus is ellipsoidal, and that of the leaflet
is cylindrical or slightly conical.

A. FUNCTIONAL IM PORTANCE OF VALVE ANATOMY

Valve anatomy has a direct bearing on valve function. With the growth of surgical procedures
and the increasing use of bioprosthetic valves it becomes important to examine how the valve
structure relates to valve function. A normal aortic valve has three leaflets, whereas a malformed
valve has only one or two leaflets. Malformed valves are more prone to disease, which
emphasizes the significance of normal design. For both malformed natural valves and bio­
prosthetic valves, deviation from normal design can compromise their performance (Chapters
8 and 9).
Until recently, the shape of aortic leaflets was considered to be hemispherical.^ Subsequently,
leaflets have been shown to be curved in only one direction which makes them cylindrical.
The cylindrical leaflet has a greater stress in the circumferential direction than in the radial
direction and consequently the structure of the leaflet is best suited to withstand stress
circumferentially (Chapters 2 and 5). The shape of the leaflet is also critical for its ability to
reverse curvature. A singly curved surface can reverse curvature more easily and with less
creasing than a doubly curved surface. Since the leaflets must reverse curvature each time the
valve opens and closes, it is advantageous for them to have a cylindrical shape rather than a
spherical shape. Hence, both the leaflet shape and the reversal of curvature must be given
important consideration when designing the valve.
Consideration of commissural height is critical in order for the valve to have a minimum
overall height. It will be shown later in this chapter that if the commissural height is zero, then
the valve has to be very tall. The line of leaflet attachment in the load-bearing portion lies in a
plane across which the leaflet reflects as it goes from the open to the closed position. The
significance of the plane of reflection is pointed out later in this chapter.
The line of leaflet attachment and the line of leaflet coaptation are the locations where the
leaflets experience maximum flexion. Maximum flexion can result in highest mechanical stress
and the most wear and tear. Therefore, leaflets can be subjected to tissue damage and valvular
pathology at these locations (Chapter 8).
The coaptation surface of the leaflet serves two important functions. Part of the coaptation
surface provides a safety margin for the valve to close without regurgitation. The remaining
coaptation surface transfers the pressure load on the central portion of the leaflet to the
commissures, as discussed later in this chapter.
The aortic leaflets, in the fresh state, have no recoil tendency to bring them into coaptation.
Instead, they lie in a collapsed open position. This is also true in vivo in a functioning valve. Most
bioprosthetic valves, however, are designed so that their leaflets spring back into the closed
position. The normal aortic leaflets are extremely flexible. In bioprostheses, chemical treatment
of the valve generally reduces leaflet flexibility. Since bioprostheses do not perform as well as
the natural valve, an understanding of the structure-function relationship can be helpful in
improving bioprostheses (Chapter 9).
As mentioned earlier, the aortic valve has been generally thought of as a passive structure
where all of its mobile components move only as a result of blood flow.^ More recently, however,
it has been shown that the commissures move outward in a passive response to pressure and the
bases move inward in an active response to myocardial contraction in systole. Commissural
movement is made possible because of the elastic walls of the sinuses which exist between the
commissures. Base movement occurs in response to the contraction of the myocardium which
occupies almost two thirds of the circumference of the valve at this level. The triple scalloped
line (the fibrous coronet) is situated between the elastic walls of the sinuses above and the left
ventricular myocardium below. It is not a ring and therefore does not prevent the valve anulus
from changing dimensions (Chapter 3).
The sinus diameter (at its maximum dimension) is almost twice that of the aorta. This cavity
plays an important role in the mechanism of valve closure (Chapter 4). An oblique section
through the leaflet-sinus assembly, taken in the circumferential plane of the leaflet, shows that
the luminal surfaces of the leaflet and the sinus together appear as a full circle (Figure 5B). This
suggests that the shape of the leaflet-sinus assembly is important in determining how stresses
8 The Aortic Valve

6R

2TTR

FIGURE 6. The total length of the leaflet free edges (6R) in this trileaflet valve is nearly equal
to the circumference of a circle.

are developed in the valve. The leaflet and the sinus together form a unit to contain the diastolic
pressure within itself. Stress continuity exists between the leaflet and the sinus and the leaflet
does not pull on the aortic wall (Chapter 5).

IV. DIMENSIONS OF THE VALVE

The normal aortic valve has three leaflets, although occasionally one, two, or four leaflets
have been seen in abnormally formed valves. A three-leaflet design is best suited for the normal
valve as explained below. For a valve located at the entrance of a circular tube, such as the aorta,
the valve should produce a circular opening so that the blood flows smoothly. When the valve
is open the circumference of the opening is 2tiR or approximately six times the radius (Figure
6). When the valve is closed, the total length of the free-edges of the three leaflets is also
approximately six times the radius. Hence, a three-leaflet valve can produce a circular opening
without going through a large change in leaflet length. Two- or four-leaflet valves, however, will
not produce a circular opening without going through a major change in leaflet length or without
producing excessive folds in the leaflets. Both of these effects will cause excessive wear and tear
on the leaflet and compromise the valve function. Hence, the three-leaflet design produces a
valve which can open and close with little change in the leaflet length and without forming folds
in the leaflet.^ From the design point of view it is important to note that one and two-leaflet human
valves have been known to become diseased more frequently than three-leaflet valves (see
Chapter 8).
Various dimensions of the aortic valve have been measured using different techniques in
 FIGURE 7. Top: Schematic presentation of the aortic valve. Bottom: Drawing of the aortic
valve showing the side view of one leaflet. Rb — radius of the base, Rc — radius of the
commissures, H — valve height, a — bottom surface angle of the leaflet, (j) — free edge angle
of the leaflet, Hs — height of the commissure, hs — sinus height, ds — radius of the outermost
wall of the sinus, Cc — coaptation height.

several mammalian species. The approaches have included measurements of excised hearts, of
silicone rubber casts of the valve, and of a functioning valve in vivo. Figure 7 shows various
dimensions that have been measured and used to describe the geometry of the valve. Although
the three leaflets are not often identical,^ they are similar enough to permit a general description
of a valve with trileaflet symmetry. The dimensions noted in Figure 7 are Rb = radius of the bases,
Rc = radius of the commissures, H = the valve height, (|) = the angle of the free edge to the plane
through the three commissures, a = the angle of the bottom surface of the leaflet to the plane
through the three commissures, Cc = coaptation height at the center, Hs = commissural height,
Lj = length of the leaflet free edge, = length of the leaflet in the radial direction, ds = sinus
depth, and hs = sinus height. Table 1 shows typical dimensions of the aortic valve (normalized
with respect to Rb) in various species. The absolute dimensions of the adult human aortic valve
are Rb = 11.3 tol4 mm, H = 15.7 to 19.8 mm, (j) = 25 to 37°, and a = 15 to 27°.^
 10 The Aortic Valve

TABLE 1
Dimensions of the Aortic Valve in Various Species (for Rb = 1)

Rc H (|)° a° Hs Lr Lr ds hs A uthors

Man 1.0 1.42 32 22 0.34 0.71 2.48 1.4 1.46 1.76 Swanson and Clark'
Man 1.34 33 2.42 Sands et al.*
Man 0.9 1.12 Lozsadi and Arvay^
Man 0.75 1.71 2.02 Reid'o
Man 2.65 1.2 Silver and Roberts’
Pig 1.3 28 2.2 Sands et al.*
Pig 1.1 1.12 Lozsadi and Arvay‘^
Pig 0.69 1.04 1.71 1.32 Reid'o
Calf 1.16 2.18 Sands et al.*
Sheep 1.08 2.13 Sands et al.*
Sheep 0.67 0.93 1.6 1.15 Reid'o
Dog 0.83 1.17 34 20 0.5 Thubrikar et al."
Dog 0.7 1.0 1.74 1.4 Reid'o
Ox 0.75 1.01 1.56 1.4 Reid'°
Rabbit 0.71 1.74 1.42 Reid'o
Range of 0.7— 1.1 1.1— 1.4 28— 34 20— 22 0.34 0.5—0.7 2.13— 2.6 1— 1.4 1.1— 1.7' 1.2— 2
values

To differentiate among the various techniques used in obtaining values reported in Table 1,
it may be noted that Swanson and Clark reported dimensions based upon a silicone rubber cast
of a closed valve prepared at 100 mmHg pressure, that Thubrikar et al. reported dimensions
based on an in vivo valve in mid-diastole, and that others reported dimensions based upon
examination of the heart at necropsy. Table 1 also lists a range of values after grouping various
species together. Considering the various techniques used, the normalized dimensions of the
valve, in a single species or in a group of species, do not appear to vary greatly. In fact, variations
in the dimensions appear to be in the range of natural variations expected in any given species.
This observation suggests that the design of the aortic valve could be the same in all mammalian
species, and, if so, the design must follow the same principles in all of them. The principles of
valve design are discussed later in this chapter.
Having noted the static dimensions of the valve, one might incorrectly think that the aortic
valve is a static structure. On the contrary, the dimensions of the aortic valve change as a function
of aortic pressure and time during each cardiac cycle, suggesting that the valve is a dynamic
structure. Swanson et al. studied changes in the dimensions as a function of aortic pressure by
preparing silicone rubber casts of closed valves at various pressures.^ The radius of the base Rb
increased about 10% when the pressure increased from 20 to 120 mmHg. The length of the leaflet
in the radial direction or the valve height H, did not change with pressure and the bottom
surface angle a increased slightly with pressure. Coaptation height Cc showed a significant
decrease when the pressure increased. The dynamic changes in the valve are considered in detail
in Chapter 3. Silver^ analyzed aortic valves from necropsy patients and found that only 16% of
the patients had three leaflets of equal size, 51 % had two leaflets of equal size, and 33% had three
leaflets of different sizes. He also reported that the sum of leaflet areas, leaflet weights, and
volumes of aortic sinuses increased with age and with heart weight. Sands^ made measurements
after closing the valve by inflating the aorta with air and then freezing the valve in liquid nitrogen
(Table 1). He reported that, in humans, about 71 % of the noncoronary leaflet and 48% of the left
coronary leaflet are continuous with the anterior leaflet of the mitral valve, and in pigs the
corresponding values are 42 and 68%.
The dimensions discussed thus far have been those of the closed valve. The dimensions of
the open valve, which relate to the dynamic changes in the valve, will be considered in detail in
Chapters 3 and 5. Briefly stated, the following dimensional changes have been noted between
 11

FIGURE 8. Schematic drawing of the aortic valve showing the design parameters: radius of the base (Rb), radius of
the commissures (Rc), valve height (H), height of the commissures (Hs), and angle of the open leaflet (p); and the
performance parameters: angle of leaflet flexion (0), minimum coaptation height (Xs), leaflet length in diastole (Ld),
and leaflet length in systole (Ls). The drawing shows the side view of one leaflet in both the closed and open positions.

the closed and the open valve. In systole, the commissures move outward by 12%, the bases
move inward by 9 to 22%, the leaflets shorten in the circumferential direction by 9% and in the
radial direction by 24%, and the centers of the sinuses move outward by about 4%. In the open
valve, the orifice is circular in early systole, and the orifice area decreases gradually during
systole.

V. PRINCIPLES OF VALVE DESIGN

We saw in the previous section that the normalized dimensions of the aortic valve were fairly
similar in various mammalian species. This suggests that there is an underlying universal
principle that governs the design of the aortic valve.
Thubrikar et al. studied the principles of valve design, establishing certain peformance
criteria and determining the design parameters which satisfied those c rite ria .T h e ir study
focused on the design of the leaflets and excluded the aortic sinuses.
The design of the aortic valve was described in terms of five parameters: radius of the base
(Rb), radius of the commissures (Rc), valve height (H), height of the commissures (Hs), and the
angle of the open leaflet to vertical (P) (Figure 8). A valve described using these parameters has
the following features: (1) the leaflets are cylindrical; (2) the free edge of the open leaflet lies
in a plane passing through the three commissures; (3) part of the line of leaflet attachment is
vertical (Hs); and (4) the remaining line of leaflet attachment lies in a plane across which the
leaflet can reflect to produce a closed valve.

A. CONSTRUCTION OF THE VALVE MODEL

To establish that the five design parameters were sufficient to construct a valve, computer-
aided design software was used to construct a valve model. For the initial construction, the values
reported for canine aortic v alv es,w h ich were Rb = 10 mm, Rc = 8.3 mm, H = 11.7 mm, Hs =
2.8 mm, and p = 5.6°, were used.
12 The Aortic Valve

To construct the valve model, a conical surface (CS) of height (H-Hs) and radii Rb and Rc
was created (Figure 9A-I). Three equidistant points were located on the upper surface and three
on the lower surface of the cone and placed 60° out of phase with each other. The upper points
represented the commissures and the lower points represented the bases of the leaflets. A plane
(P) passing through two commissures and a base was allowed to intersect with the conical
surface and the excess material above the plane was removed (Figure 9A-I and II). The line of
intersection of the plane with the conical surface represented the line of attachment (L) of the
pressure-bearing part of the leaflet. The plane itself represented the plane of reflection of the
leaflet. This intersection was repeated to create similar planes for the other two leaflets (Figure
9A-III). Then three vertical lines of height (Hs) were drawn at the commissures (Figure 9A-IV).
These lines represented the attachment of the redundant part of the leaflet. This completed the
construction of the entire leaflet attachment to the aortic wall.
To construct the free edge of the leaflet, a line was drawn from the base at P° angle to the
vertical and allowed to intersect a plane (P') passing through the top of the commissures (Figure
9A-V). This point of intersection (M) and the two adjacent commissures were then used to draw
an arc of a circle which represented the free edge (FE) (Figure 9A-VI). The leaflet was
constructed as a surface bounded by the free edge and the line of attachment (Figure 9A-VI). The
other two leaflets were constructed in a similar fashion, thus completing the construction of the
open valve (Figure 9A-VII).
To construct the closed valve, the leaflets were reflected across the plane of reflection (P) and
allowed to intersect with each other (Figure 9B-VIII). The line of intersection (LI) represented
the line of leaflet coaptation (Figure 9B-IX). The leaflet above this line was eliminated, leaving
only the pressure-bearing part. To construct the coaptation surface, a vertical line of length Xs
was drawn at the center of the valve (Figure 9B-X). The length Xs was chosen so that the radial
length of the leaflet in the closed valve would be equal to that in the open valve. The free edges
were constructed as straight lines joining the upper points of Xs and Hs (Figure 9B-X and XI).
(Xs in Figure 8 is the same as Cc in Figure 7.) This completed the construction of the closed valve
(Figure 9B-XII).
To determine the adequacy of valve closure, the length of the leaflet free edge in the closed
valve was compared with that in the open valve. If the length of the free edge was greater in the
open valve than in the closed valve, then there was too much leaflet material which would
produce folds in the closed valve. If the length of the free edge was less in the open valve than
in the closed valve, then there was not enough leaflet material for closure, which would produce
an incompetent valve.

B, VALVES OF VARIOUS DESIGNS

Thubrikar et al. also demonstrated that choosing the design parameters empirically will not
produce a better valve. To prove this point, they constructed several valve models by choosing
the parameters empirically. Table 2 shows the design parameters and functional problems
associated with these valves. Figure 10 shows graphically the problems associated with function
of some of the valves. For example, decreasing only the ratio Rb/Rc results in a tall valve, and
increasing the ratio results in an incompetent valve. Decreasing only the valve height (H) results
in an incompetent valve, and increasing only the commissural height (Hs) or decreasing only the
angle p results in a valve which has incomplete coaptation. Hence, a change in any one design
parameter is not enough to produce a better valve, but this change must be accompanied by
changes in the other parameters. Furthermore, a logical approach must be developed for
determination of the design parameters of an ideal valve.

C. PERFORMANCE CRITERIA
For the valve to give optimum performance, the following criteria were specified: (1) a
certain minimum coaptation height, (2) no folds in the leaflet, (3) minimum valve height, and
 13

HE

FIGURE 9. (A) Schematic drawings to show steps in construction of a model of an open aortic
valve. I — CS represents a conical surface of radii Rc and Rb and height (H-Hs). P represents
a plane passing through two commissures and a base, and intersecting with CS along the line
of intersection L. II — Portion of CS beyond line L is removed. Ill — Procedure in II is repeated
for all three leaflets. IV — B is the base of radius Rb. A vertical line of height Hs is added at
the commissures. This skeleton also represents the stent of a trileaflet bioprosthetic valve. V —
a line drawn from the base at an angle p intersects a plane P', passing through the commissures,
at a point M. VI — Free edge FE is a circular arc passing through M and two adjacent
commissures. The leaflet is a surface bounded by the free edge and the line of attachment. VII
— computer constructed model of the open valve.(9B) Steps showing construction of a closed
valve model. VIII — Open leaflet OL is reflected across the plane P to produce reflected leaflet
RL. M ' is the mirror image of M. IX — Upon reflection, all three leaflets intersect with each
other along a line of intersection LI. The shaded portion above LI is deleted. X —^At the valve
center, a line of height Xs is constructed. Then the lines are drawn from the upper points of
commissures to the upper point of Xs. This gives a shaded portion which represents the
redundant portion of the leaflet. This shaded portion has outer dimensions similar to those in
Figure IX. XI — All three leaflets are shown in the closed position, RL and LL represent
redundant leaflet and load-bearing leaflet, respectively. XII — Computer constructed model of
the closed valve.
14 The Aortic Valve

-LI

XE

XIL

FIGURE 9B

TABLE 2
Effect of Design Parameters on Valve Function

Design parameters

# Valve type Rb/Rc H/Rc Hs/Rc Function

1. Natural valve (dog) 1.20 1.40 0.29 5.6 Normal

2. Valve model (RcT) 1.00 1.40 0.29 5.6 Too tall
3. Valve model (R ei) 1.40 1.40 0.29 5.6 Incompetent
4. Valve model (H i) 1.20 1.20 0.29 5.6 Incompetent
5. Valve model ( H i i ) 1.20 1.00 0.29 5.6 Incompetent
6. Valve model (H st) 1.20 1.40 0.40 5.6 Incomplete coaptation
7. Valve model (p i) 1.20 1.40 0.29 0.0 Incomplete coaptation

(4) minimum leaflet flexion. The first criterion provided a safety factor for closure, thereby
assuring a competent valve. A minimum coaptation height equal to 10% of the radius of the base
was selected, i.e., Xs - 0.1 Rb (Figure 8). The second criterion eliminated stresses due to leaflet
folding and was achieved by making the length of the leaflet free edge the same in systole and
diastole, i.e., Ls = Ld (Figure 8). The third criterion (low profile) reduced dead space. The fourth
criterion reduced flexion stresses and conserved energy by minimizing leaflet motion.

D. GEOMETRIC RELATIONSHIPS
To determine the design parameters for an optimal valve, geometric relationships were
developed between the design parameters Rb, Rc, H, Hs, and P and the performance parameters
Ls, Ld, Xs, and 0 where 0 represented the angle of leaflet flexion (Figure 8). The performance
parameters were chosen to enforce the performance criteria. The geometric relationships were
(see Appendix I for derivation):
 15

FIGURE 10. Computer constructed models of trileaflet valves. A — canine aortic valve, B — valve model of lower
height, C — valve model of increased commissural height. A, B, and C correspond to valves numbered 1,5, and 6 in
Table 2. B shows the top view of an incompetent valve and C shows incomplete coaptation because there is not enough
Xs at the center of the valve.

H - Hs
e° = 180 + 2p - 2 ta n -‘
iRb -

Rb
X. =
cosp
H - Hs
sin p - 2 ta n -‘l _ Rc

1- - - - - - - - r / \ n 2
1 - Hs \
Ld —
Rc^ + ■H - Xs - Rb • tan 2tan M Rc - P - 90 >-
Rb
L \ 2 /
V 3 • Rc
2Rb + 2Htan(3 - Rc )]
sinj^2tan
V 3 • Rc
2Rb + 2Htanp - Rc )]
E. PROCESS OF OPTIMIZATION
For the optimal valve, the performance criteria were Xs = 0.1 Rb, Ls = Ld, minimum H, and
minimum 0. When the above-noted relationships were explored, it was found that the two
performance criteria, minimum height and minimum flexion, opposed each other. Figure 11
shows plots of p vs. H and 0 for various Rc. This plot was used to determine the design
parameters for the optimal valve.
Why Rc should be less than Rb — For any given P the valve height is maximum when Rc
16 The Aortic Valve

DESIGN PARAMETERS (Rb, Rc, H, Hs, 3)

FIGURE 11. Plot of valve height (H) and leaflet flexion angle 0 vs. design parameter (p) for various values of Rc.
Rb is constant. For a given Rc, H decreases and 6 increases as p increases. For a given p, H decreases and 0 increases
as Rc decreases. Optimum design parameters are Rb = 10 mm, Rc = 8 to 10 mm, H = 11.5 mm, Hs = 2.4 to 2.6 mm,
and p = 4 to 11°.

= Rb (Figure 11). As Rc decreases the valve height decreases. Hence, the main advantage of Rc
being less than Rb is the reduction of valve height. It should be stated that too much reduction
in Rc (e.g., Rc = 7 mm or 6 mm, for Rb = 10 mm) produces an obstructive valve, allowing the
commissures to project too far into the blood stream.
Why P should be greater than zero — For a perfectly cylindrical flow conduit, p = 0, and
the valve height is maximum (Figure 11). Hence, for p of positive value (1 to 10°), a valve of
lower height is obtained. The greatest reduction in height occurs for smaller values of p.
Why Hs should be greater than zero — The importance of Hs (the commissural height) has
been emphasized by the results of the study by Thubrikar et al. They observed that for Hs = 0
only a very tall valve was possible, and for Hs = 1,2 or 3 mm, a valve of greatly reduced height
was obtained. Hence, each of the design parameters Rc, P and Hs contributed to a reduction in
the valve height H.

F. THE DESIGN OF THE NATURAL AORTIC VALVE

For Rb = 10 mm, let the minimum height be 11.5 mm, as shown by a line in Figure 11, and
examine the design parameters. The possible design parameters are p = 4° and Rc = 8 mm, or
P = 8° and Rc = 9 mm, or p = 11° and Rc = 10 mm. For these designs, Hs ranges from 2.4 to 2.6
mm. The resulting design parameters for an aortic valve of Rb = 10 mm are H = 11.5 mm, Hs
= 2.4 to 2.6 mm, Rc = 8 to 10 mm, and p = 4 to 11° and the accompanying flexion angle is 75
to 80°. The resultant design of the model aortic valve is therefore quite specific. These results
 17

TABLE 3
Design Parameters of the Aortic Valve (for Rb = 10 mm)

Valve H (mm) Rc (mm) Hs (mm) A uthors

Optimal valve 11.5 8— 10 2.4— 2.6 4— 11° Thubrikar et al.'^

Man 14.2 10.0 7.1 0 Swanson and Clark^
Man 13.4 — — — Sands et al.^
Man — 9.0 — — Lozsadi and Arvay^
Man — 7.5 — — Reid'^
Pig 13.0 — — — Sands et al.^
Pig — 11.0 — — Lozsadi and Arvay*^
Pig ' — 6.9 — — Reid^®
Calf 11.6 — — — Sands et al.^
Sheep 10.8 — — — Sands et al.^
Dog 11.7 8.3 5.0 5 Thubrikar et al.' ’

show that among various mammalian species the basic design of the aortic valve must be similar.
Table 3 compares the design parameters of the aortic valve in several species to those of the
optimal valve. The comparison indicates that the optimal valve and the natural aortic valve have
similar design parameters. In other words, the design of the natural aortic valve is based upon
the principles of optimum performance. This principle of valve design must hold true for any
trileaflet valve, including the natural pulmonary valve and all trileaflet prostheses.

G. THE EFFECT OF DIMENSIONAL CHANGES

In the model of Thubrikar et al., the dimensions of the valve were assumed to be constant.
Although the natural aortic valve undergoes dimensional changes during a cardiac cycle (see
Chapter 3), these cyclic changes do not alter the concept of the basic design. Let us consider the
dimensional changes observed in vivo{\) the commissures of the aortic valve move outward in
systole by 12%;’^(2) the bases of the aortic valve leaflets move inward in systole by 9 to 22%;"^
(3) the leaflet length shortens circumferentially by 9% in systole; and (4) the leaflet length
shortens radially by 24% in systole, or lengthens by 31 % from systole to diastole.'^ Now let us
examine whether the present valve model would remain functional and efficient if it were to
undergo the above-mentioned dimensional changes. Suppose that the design of the valve model
is valid in diastole and that the dimensional changes occur in systole. The present valve model
has a conical support structure because Rc is less than Rb. In systole, the outward movement of
the commissures and the inward movement of the base will make the support structure more
cylindrical (Figure 12). Ih e present valve model has an angle p of 4 to 11°, which makes the
valve opening slightly funnel like. In systole, shoitening of the leaflet length in both the
circumferential and radial directions makes the flow conduit cylindrical (Figure 12). Hence, all
of the dimensional changes, when considered to occur in systole, result in an even more
favorable flow conduit.

II. THE ROLE OF THE COAPTING SURFACE OF THE LEAFLET

The study indicates that the minimum coaptation height Xs occurs at the center of the valve
which provides a safety margin against valvular regurgitation. Part of the coapting surface (area
R1 in Figure 13) serves to provide the height Xs. The remaining coapting surface (area R2 in
Figure 13) sustains the load of the closing pressure on the central portion of the leaflet (area FI L
in Figure 13). The central portion of the load bearing leaflet has no support other than its
attachment to the commissures through this coapting surface. If all of the coapting area was
removed, the valve would be incompetent. Therefore, this area should not be called the
redundant portion of the leaflet. Perforations in the coapting surface can be tolerated as long as
the coapting surface can transmit the load of the closing pressure from the central portion of the
leaflet to the aortic wall.'^ The coaptation area also provides a surface seal rather than a line seal.
18 The Aortic Valve

Rc Lc

'i LR

FIGURE 12. Effect of dimensional changes on valve performance. Left arrow indicates the
direction of blood flow. In systole, when Rc moves outward, Rb moves inward, circumferential
length of the leaflet Lc decreases, and radial length of the leaflet L^^ decreases; even then, the
flow conduit remains cylindrical. The shaded area represents the surface of one open leaflet after
the dimensional changes.

In the natural valve, because dimensional changes occur in vivo, it may be necessary to have
an extra margin of safety against regurgitation. Therefore, the valve may have greater Xs than
the model valve (Figure 13). Also, in the natural valve the line of leaflet coaptation may move
up and down in response to the dimensional changes.
 19

Hs
XXs

FIGURE 13. Illustration shows the role of the coapting surface of the
leaflet. The coapting surface R1 is required to provide the coaptation height
Xs. The coapting surface R2 is required to support the load on the area ELL,
which represents a fraction of the load-bearing leaflet. Hs (commissural
height) represents the attachment of the coapting surface.

REFERENCES
1. Swanson, W. M. and Clark, R. E., Dimensions and geometric relationships of the human aortic valve as a
function of pressure, Circ. Res., 35, 871, 1974.
2. Netter, F. H., Ciba Collection o f Medical Illustrations: Heart, Voi. 5, Ciba Pharmaceutical Co., Summit, NJ,
1978, 12.
3. Mercer, J. L., Benedicty, M., and Bahnson, H. T., The geometry and construction of the aortic leaflet, J.
Thorac. Cardiovasc. Surg., 65, 511, 1973.
4. Robel, S. B., Structural mechanics of aortic valve, in Prosthetic Replacement o f the Aortic Valve, Sauvage, L.
R., Viggers, R. F., Berger, K., Robel, S. B., Sawyer, P. N., and Wood, S. J., Eds., Charles C Thomas, Springfield,
IL, 1972, 30.
5. Zimmerman, J., The functional and surgical anatomy of the aortic valve. Cardiac Surg., 5, 862, 1969.
20 The Aortic Valve

6. Davila, J. C., The mechanics of the cardiac valves: considerations pertinent to the design and construction of
prostheses, in Prosthetic Valves for Cardiac Surgery, Merendino, K. A., Morrow, A. G., Lillehei, C. W., and
Muller, W. H., Jr., Eds., Charles C Thomas, Springfield, IL, 1961, 9.
7. Silver, M. A. and Roberts, W. C., Detailed anatomy of the normally functioning aortic valve in hearts of
normal and increased weight. Am. J. Cardiol., 55, 454, 1985.
8. Sands, M. P., Rittenhouse, E. A., Mohri, H., and Merendino, K. A., An anatomical comparison of human,
pig, calf, and sheep aortic valves, Ann. Thorac. Surg., 8, 407, 1969.
9. Lozsadi, K. and Arvay, A., Comparative anatomical investigations on the heterotransplantation of the aortic
valve, Acta Chir. Acad. Sci. Hung., 10, 207, 1969.
10. Reid, K., The anatomy of the sinus of Valsalva, Thorax, 25, 79, 1970.
11. Thubrikar, M., Piepgrass, W. C., Shaner, T. W., and Nolan, S. P., The design of the normal aortic valve.
Am. J. Physiol., 241, H795, 1981.
12. Thubrikar, M. J., Samanta, S., and Nolan, S. P., The principles of aortic valve design, Trans. Am. Soc. Artif.
Intern. Organs, submitted.
13. Thubrikar, M., Harry, R., and Nolan, S. P., Normal aortic valve function in dogs. Am. J. Cardiol, 40, 563,
1977.
14. Thubrikar, M., Nolan, S. P., Bosher, L. P., and Deck, J. D., The cyclic changes and structure of the base of
the aortic valve. Am. Heart J., 99, 217, 1980.
15. Thubrikar, M., Piepgrass, W. C., Bosher, L. P., and Nolan, S. P., The elastic modulus of canine aortic valve
leaflets in vivo and in vitro, Circ. Res., 47, 792, 1980.
16. Thubrikar, M. J., Aouad, J., and Nolan, S. P., Comparison of the in vivo and in vitro mechanical properties
of aortic valve leaflets, J. Thorac. Cardiovasc. Surg., 92, 29, 1986.
17. McAlpine, W. A., Heart and Coronary Arteries, Springer-Verlag, New York, 1975, 23.
Geometry of the Aortic Valve
Swanson, W.M. and Clark, R.E. , Dimensions and geometric relationships of the human aortic valve as a
function of pressure, Circ. Res., 35, 871, 1974.
Netter, F.H. , Ciba Collection of Medical Illustrations: Heart, Vol. 5, Ciba Pharmaceutical Co., Summit, NJ,
1978, 12.
Mercer, J.L. , Benedicty, M. , and Bahnson, H.T. , The geometry and construction of the aortic leaflet, J.
Thorac. Cardiovasc. Surg., 65, 511, 1973.
Robel, S.B. , Structural mechanics of aortic valve, in Prosthetic Replacement of the Aortic Valve, Sauvage,
L.R. , Viggers, R.F. , Berger, K. , Robel, S.B. , Sawyer, P.N. , and Wood, S.J. , Eds., Charles C Thomas,
Springfield, IL, 1972, 30.
Zimmerman, J. , The functional and surgical anatomy of the aortic valve, Cardiac Surg., 5, 862, 1969.
Davila, J.C. , The mechanics of the cardiac valves: considerations pertinent to the design and construction of
prostheses, in Prosthetic Valves for Cardiac Surgery, Merendino, K.A. , Morrow, A.G. , Lillehei, C.W. , and
Muller, W.H., Jr. , Eds., Charles C Thomas, Springfield, IL, 1961, 9.
Silver, M.A. and Roberts, W.C. , Detailed anatomy of the normally functioning aortic valve in hearts of normal
and increased weight, Am. J. Cardiol., 55, 454, 1985.
Sands, M.P. , Rittenhouse, E.A. , Mohri, H. , and Merendino, K.A. , An anatomical comparison of human, pig,
calf, and sheep aortic valves, Ann. Thorac. Surg., 8, 407, 1969.
Lozsadi, K. and Arvay, A. , Comparative anatomical investigations on the heterotransplantation of the aortic
valve, Acta Chir. Acad. Sci. Hung., 10, 207, 1969.
Reid, K. , The anatomy of the sinus of Valsalva, Thorax, 25, 79, 1970.
Thubrikar, M. , Piepgrass, W.C. , Shaner, T.W. , and Nolan, S.P. , The design of the normal aortic valve, Am.
J. Physiol., 241, H795, 1981.
Thubrikar, M.J. , Samanta, S. , and Nolan, S.P. , The principles of aortic valve design, Trans. Am. Soc. Artif.
Intern. Organs, submitted.
Thubrikar, M. , Harry, R. , and Nolan, S.P. , Normal aortic valve function in dogs, Am. J. Cardiol., 40, 563,
1977.
Thubrikar, M. , Nolan, S.P. , Bosher, L.P. , and Deck, J.D. , The cyclic changes and structure of the base of
the aortic valve, Am. Heart J., 99, 217, 1980.
Thubrikar, M. , Piepgrass, W.C. , Bosher, L.P. , and Nolan, S.P. , The elastic modulus of canine aortic valve
leaflets in vivo and in vitro, Circ. Res., 47, 792, 1980.
Thubrikar, M.J. , Aouad, J. , and Nolan, S.P. , Comparison of the in vivo and in vitro mechanical properties of
aortic valve leaflets, J. Thorac. Cardiovasc. Surg., 92, 29, 1986.
McAlpine, W.A. , Heart and Coronary Arteries, Springer-Verlag, New York, 1975, 23.

Histology and Cytology of the Aortic Valve*

Luschka, H. , Die Structur der halbmondförmigen Klappen des Herzens, Arch. Physiol. Heilk., 537, 1856.
Joseph, L. , Über die Ringe und Klappen des menschlichen Herzens, Virch. Arch. Pathol. Anat., 14, 244,
1858.
Luchsinger, B. , Zur Architectur der Semilunarklappen, Arch. Ges. Physiol. Menschen Tiere, 34, 291, 1884.
Curtis, F. , De la structure des valvules sigmoides de l’aorte et de l’artère pulmonaire, C.R. Soc. Biol., 8, 591,
1888.
Veraguth, O. , Untersuchungen über normale und entzündete Herzklappen, Virch. Arch. Pathol. Anat., 139,
59, 1895.
Mönckeberg, J.G. , Der normale histologische Bau und die Sklerose der Aortenklappen, Virch. Arch. Pathol.
Anat., 176, 472, 1904.
Dewitzky, W.I. , Über den Bau und die Entstehung verschiedener Former der chronischen Veränderungen in
den Herzklappen, Virch. Arch. Pathol. Anat., 199, 273, 1910.
Gross, L. and Kugel, M.A. , Topographie anatomy and histology of the valves in the human heart, Am. J.
Pathol., 7, 445, 1931.
Clark, R.E. and Finke, E.H. , Scanning and light microscopy of human aortic leaflets in stressed and relaxed
states, J. Thorac. Cardiovasc. Surg., 67, 792, 1974.
Brewer, R.J. , Mentzer, R.M. , Deck, J.D. , Ritter, R.C. , Trefil, J.S. , and Nolan, S.P. , An in vivo study of the
dimensional changes of the aortic valve leaflets during the cardiac cycle, J. Thorac. Cardiovasc. Surg., 74,
645, 1977.
Pepper, O.H.P. , Medical Etymology, W.B. Saunders, Philadelphia, 1949, 17.
Debrunner, U.H. , Der funktionelle Bau der arterioventrikularklappen des Menschen, Acta Anat., 7, 132, 1949.
Puff, A. , Funktionelle Anatomie des Herzklappenapparates, Verhandl. Dtsch. Ges. Kreislaufforschg., 31, 1,
1965.
Zimmerman, J. , The functional and surgical anatomy of the aortic valve, Israel J. Med. Sci., 5, 862, 1969.
Thubrikar, M. , Harry, R. , and Nolan, S.P. , Normal aortic valve function in dogs, Am. J. Cardiol., 40, 563,
1977.
Thubrikar, M. , Bosher, L.P. , and Nolan, S.P. , The mechanism of opening of the aortic valve, J. Thorac.
Cardiovasc. Surg., 77, 863, 1979.
Thubrikar, M. , Nolan, S.P. , Bosher, L.P. , and Deck, J.D. , The cyclic changes and structure of the base of
the aortic valve, Am. Heart J., 99, 217, 1980.
Jahnke, A. , Elektronenmikroskopische Untersuchungen über die Intercellularsubstanz der menschlichen
Aortenklappen, Virch. Arch. Pathol. Anat., 329, 486, 1956.
Kühnel, W. , Elektronenmikroskopische Untersuchungen an den Herzklappen, Experientia, 21, 535, 1965.
Kühnel, W. , Elektronenmikroskopische Untersuchungen über den unterschiedlichen Bau der Herzklappen. I.
Mitteilung. Mitralis und Aortenklappe, Z. Zellforsch., 69, 452, 1966.
Kühnei, W. , Elektronenmikroskopische Untersuchungen über den unterschiedlichen Bau der Herzklappen. II.
Mitteilung. Tricuspidalis und Pulmonalisklappe, Z. Zellforsch., 72, 462, 1966.
Torii, S. , Bashey, R.I. , and Nakao, K. , Acid mucopolysaccharide composition of human heart valve,
Biochim. Biophys. Acta, 101, 285, 1965.
Nakao, K. , Mao, P. , Ghidoni, J. , and Angrist, A. , An electron microscopic study of the aging process in the
rat heart valve, J. Gerontol., 21, 72, 1966.
Bashey, R.I. , Torii, S. , and Angrist, A. , Age-related collagen and elastin content of human heart valves, J.
Gerontol., 22, 203, 1967.
Ferrans, V.J. , Spray, T.L. , Billingham, M.E. , and Roberts, W.C. , Ultrastructure of Hancock porcine valvular
heterografts. Pre-and post-implantation changes, Circulation, 58 (Suppl. 1), 110, 1977.
Ferrans, V.J. , Spray, T.L. , Billingham, M.E. , and Roberts, W.C. , Structural changes in glutaraldehyde-
treated porcine heterografts used as substitute cardiac valves. Transmission and scanning electron
microscopic observations in 12 patients, Am. J. Cardiol., 41, 1159, 1978.
Ferrans, V.J. , Boyce, S.W. , Billingham, M.E. , Jones, M. , Ishihara, T. , and Roberts, W.C. , Calcific deposits
in porcine bioprostheses: structure and pathogenesis, Am. J. Cardiol., 46, 721, 1980.
Fishbein, M.C. , Levy, R.J. , Ferrans, V.J. , Dearden, L.C. , Nashef, A. , Goodman, A.P. , and Carpentier, A. ,
Calcifications of cardiac valve bioprostheses. Biochemical, histologic, and ultrastructural observations in a
subcutaneous implantation model system, J. Thorac. Cardiovasc. Surg., 83, 602, 1982.
Valente, M. , Bortolotti, U. , and Thiene, G. , Ultrastructural substrates of dystrophic calcification in porcine
bioprosthetic valve failure, Am. J. Pathol., 119, 12, 1985.
Thubrikar, M. , Nolan, S.P. , Bosher, L.P. , and Deck, J.D. , The cyclic changes and structure of the base of
the aortic valve, Am. Heart J., 99, 217, 1980.
McAlpine, W.A. , Heart and Coronary Arteries, Springer-Verlag, New York, 1975.
Sauren, A.A.H.S. , The Mechanical Behaviour of the Aortic Valve, Doctoral thesis, Eindhoven University of
Technology, Eindhoven, Netherlands, 1981.
Broom, N. and Christie, G.W. , The structure/function relationship of fresh and glutaraldehyde-fixed aortic
valve leaflets, in Cardiac Bioprostheses, Cohn, L.H. and Gallucci, V. , Eds., Yorke Medical Books, New York,
1982, 477.
Lyons, M.F. , Ultrastructural organization in the aortic valve of the dog, Anat. Rec., 184, 467, 1976.
Simionescu, N. and Simionescu, M. , The cardiovascular system, in Histology. Cell and Tissue Biology, 5th
ed., Weiss, L. , Ed., Elsevier Biomedical, New York, 1983, 371.
Ernst, V.E. , Drommer, W. , Schneider, P. , and Trautwein, G. , Elektronenmikroskopische Untersuchungen
zur Normalstruktur der Atrioventrikularklappen des Hundes, Anat. Anz., 134, 309, 1973.
Mitomo, Y. , Nakao, K. , and Angrist, A. , The fine structure of the heart valves in the chicken. I. Mitral valve,
Am. J. Anat., 125, 147, 1969.
Glagov, S. , Grande, J. , Vesselinovitch, D. , and Zarins, C.K. , Quantitation of cells and fibers in histologic
sections of arterial walls: advantages of contour tracing on a digitizing plate, in Connective Tissues in Arterial
and Pulmonary Disease, McDonald, T.F. and Chandler, A.B. , Eds., Springer-Verlag, New York, 1981, 57.
Ross, R. and Bornstein, P. , The elastic fiber. I. The separation and partial characterization of its macromol-
ecular components, J. Cell Biol., 40, 366, 1969.
Mori, Y. , Bashey, R.I. , and Angrist, A. , The in vitro biosynthesis of collagen in bovine heart valves, Fed.
Proc., 27, 476, 1968.
Schneider, P.J. and Deck, J.D. , Tissue and cell renewal in the natural aortic valve of rats: an
autoradiographic study, Cardiovasc. Res., 15, 181, 1981.
Hurle, J.M. , Colvee, E. , and Fernandez-Teran, M.A. , The surface anatomy of the human aortic valve as
revealed by scanning electron microscopy, Anat. Embryol., 172, 61, 1985.
Deck, J.D. , Endothelial cell orientation on aortic valve leaflets, Cardiovasc. Res., 20, 760, 1986.
Deck, J.D. , Orientation of endothelial cells on surfaces of aortic valve leaflets in dogs, Anat. Rec., 193, 518,
1979.
Low, F.N. , Microfibrils: fine filamentous components of the tissue space, Anat. Rec., 142, 131, 1962.
Haust, M.D. , Fine fibrils of extracellular space (microfibrils), Am. J. Pathol., 47, 1113, 1965.
Filip, D.A. , Radu, A. , and Simionescu, M. , Interstitial cells of the heart valves possess characteristics similar
to smooth muscle cells, Circ. Res., 59, 310, 1986.
Ryan, G.B. , Cliff, W.J. , Gabbiani, G. , Irlé, C. , Montandon, D. , Statkov, P.R. , and Majno, G. ,
Myofibroblasts in human granulation tissue, Hum. Pathol., 5, 55, 1974.
Majno, G. , Gabbiani, G. , Hirschel, B.J. , Ryan, G.B. , and Statkov, P.R. , Contraction of granulation tissue in
vitro: similarity to smooth muscle, Science, 173, 548, 1971.
Jester, J.V. , Rodrigues, M.M. , and Herman, I.M. , Characterization of avascular corneal wound healing
fibroblasts: new insights into the myofibroblast, Am. J. Pathol., 127, 140, 1987.
Deck, J.D. , Thubrikar, M.J. , Schneider, P.J. , and Nolan, S.P. , Structure, stress, and tissue repair in aortic
valve leaflets, Cardiovasc. Res., 22, 7, 1988.
McGregor, C.G.A. , Bradley, J.F. , McGee, J.O.D. , and Wheatley, D.J. , Viability in human heart valves
prepared for grafting, Cardiovasc. Res., 10, 394, 1976.

Dynamics of the Aortic Valve

Stein, P.D. , Roentgenographic method for measurement of the cross-sectional area of the aortic valve, Am.
Heart J., 81, 622, 1971.
Thubrikar, M. , Carabello, B.A. , Aouad, J. , and Nolan, S.P. , Interpretations of aortic root angiography in
dogs and in humans, Cardiovasc. Res., 16, 16, 1982.
Thubrikar, M. , Harry, R. , and Nolan, S.P. , Normal aortic valve function in dogs, Am. J. Cardiol., 40, 563,
1977.
van Steenhoven, A.A. , Verlaan, C.W.J. , Veenstra, P.C. , and Reneman, R.S. , In vivo cinematographic
analysis of behavior of the aortic valve, Am. J. Physiol., 240, H286, 1981.
Hider, C.F. , Taylor, D.E.M. , and Wade, J.D. , Action of the mitral and aortic valves in vivo studied by
endoscopic cine photography, Q.J. Exp. Physiol., 51, 372, 1966.
Padula, R.T. , Cowan, G.S.M. , and Camishion, R.C. , Photographic analysis of the active and passive
components of cardiac valvular action, J. Thorac. Cardiovasc. Surg., 56, 790, 1968.
Brewer, R.J. , Deck, J.D. , Capati, B. , and Nolan, S.P. , The dynamic aortic root, J. Thorac. Cardiovasc.
Surg., 72, 413, 1976.
Thubrikar, M. , Bosher, L.P. , and Nolan, S.P. , The mechanism of opening of the aortic valve, J. Thorac.
Cardiovasc. Surg., 77, 863, 1979.
von Bernuth, G. , Tsakiris, A.G. , and Wood, E.H. , Effects of variations in the strength of left ventricular
contraction on aortic valve closure in the dog, Circ. Res., 28, 705, 1971.
Tsioulias, T. , Calibre variations in the left ventricular outflow tract, Acta Radiol. Diag., 3, 209, 1965.
Thubrikar, M. , Nolan, S.P. , Bosher, L.P. , and Deck, J.D. , The cyclic changes and structure of the base of
the aortic valve, Am. Heart J., 99, 217, 1980.
Hinds, J.E. , Hawthorne, E.W. , Mullins, C.B. , and Mitchell, J.H. , Instantaneous changes in the left
ventricular lengths occurring in dogs during the cardiac cycle, Fed. Proc., 28, 1351, 1969.
McAlpine, W.A. , Heart and Coronary Arteries, Springer-Verlag, New York, 1975, 10.
Spaan, J.A.E. , van Steenhoven, A.A. , Schaar, P.J. v. d. , Dongen, M.E.H. v. , Smulders, P.T. , and Leliveld,
W.H. , Hydrodynamical factors causing large mechanical tension peaks in leaflets of artificial triple leaflet
valves, Trans. Am. Soc. Artif. Int. Organs, 21, 396, 1975.
Chaillet, J.L. , Communication 468, III Congress Mondial de Cardiologie Bruxelles, 1958; Drukerij, J.D.,
Cineradiography of Cardiac Valves in Man, Van der Horst, Utrecht, 1965.
Mercer, J.L. , Movement of the aortic annulus, Br. J. Radiol., 42, 623, 1969.
Thubrikar, M. , Piepgrass, W.C. , Shaner, T.W. , and Nolan, S.P. , The design of the normal aortic valve, Am.
J. Physiol, 241, H795, 1981.
Trenkner, M. , Raczynski, S. , and Gutkowski, R. , Optimal diameter of the stent for aortic valvular grafts, J.
Thorac. Cardiovasc. Surg., 72, 613, 1976.
Swanson, W.M. and Clark, R.E. , Dimensions and geometric relationships of the human aortic valve as a
function of pressure, Circ. Res., 35, 871, 1974.
Mercer, J.L. , The movements of the dog’s aortic valve studied by high speed cineangiography, Br. J. Radiol.,
46, 344, 1973.
Ross, J., Jr. , Sonnenblick, E.H. , Covell, J.W. , Kaiser, G.A. , and Spiro, D. , The architecture of the heart in
systole and diastole: technique of rapid fixation and analysis of left ventricular geometry, Circ. Res., 21, 409,
1967.
Robel, S.B. , Wood, S.J. , and Sauvage, L.R. , The effect of pressure on the configuration of the aortic valve,
Trans. Am. Soc. Artif. Int. Organs, 10, 218, 1964.
Tsakiris, A.G. , Amorim, D.S. , and Wood, E.H. , Effect of cardiac arrhythmias on aortic valve closure studied
by roentgen video-densitometry, Mayo Clin. Proc., 44, 793, 1969.
Fluid Dynamics of the Aortic Valve
Keele, K.D. , Leonardo da Vinci on Movement of the Heart and Blood, Harvey and Blythe, London, 1952.
Henderson, Y. and Johnson, F.E. , Two modes of closure of the heart valves, Heart, 4, 69, 1912.
Lee, C.S.F. and Talbot, L. , A fluid-mechanical study of the closure of heart valves, J. Fluid Mech., 91, 41,
1979.
Wippermann, F.K. , On the fluid dynamics of the aortic valve, J. Fluid Mech., 159, 487, 1985.
Hung, T.-K. and Schuessler, G.B. , An analysis of the hemodynamics of the opening of aortic valves, J.
Biomech., 10, 597, 1977.
Swanson, W.M. and Clark, R.E. , Aortic valve leaflet motion during systole, Circ. Res., 32, 42, 1973.
Bellhouse, B.J. , The fluid mechanics of the aortic valve, in Biological Tissue in Heart Valve Replacement,
Ionescu, M.I. , Ross, D.N. , and Wooler, G.H. , Eds., Butterworths, London, 1972, chap. 2.
Bellhouse, B.J. , Velocity and pressure distributions in the aortic valve, J. Fluid Mech., 37, 587, 1969.
Bellhouse, B.J. and Talbot, L. , The fluid mechanics of the aortic valve, J. Fluid Mech., 35, 721, 1969.
Bellhouse, B.J. , The fluid mechanics of aortic and mitral valves, in Developments in Biomedical Engineering,
Black, M.M. , Ed., Crane, Russak, New York, 1972, 202.
van Steenhoven, A.A. and van Dongen, M.E.H. , Model studies of the closing behaviour of the aortic valve, J.
Fluid Mech., 90, 21, 1979.
van Steenhoven, A.A. and van Dongen, M.E.H. , The role of the trapped sinus vortex in aortic valve closure,
Biofluid Mech., 2, 317, 1980.
van Steenhoven, A.A. and Veenstra, P.C. , The effect of some hemodynamic factors on the behaviour of the
aortic valve, J. Biomech., 15, 941, 1982.
van Steenhoven, A.A. , Verlaan, C.W.J. , Veenstra, P.C. , and Reneman, R.S. , In vivo cinematographic
analysis of behavior of the aortic valve, Am. J. Physiol., 240, H286, 1981.
Peskin, C.S. and Wolfe, A.W. , The aortic sinus vortex, Fed. Proc., 37, 2784, 1978.
Peskin, C.S. , Flow patterns around heart valves: a numerical method, J. Comput. Phys., 10, 252, 1972.
Bellhouse, B.J. , Bellhouse, F. , Abbott, J.A. , and Talbot, L. , Mechanism of valvular incompetence in aortic
sinus dilatation, Cardiovasc. Res., 7, 490, 1973.
McDonald, D.A. , Blood Flow in Arteries, Williams and Wilkins, Baltimore, 1974, 110.
Falsetti, H.L. , Kiser, K.M. , Francis, G.P. , and Belmore, E.R. , Sequential velocity development in the
ascending and descending aorta of the dog, Circ. Res., 31, 328, 1972.
Stein, P.D. and Sabbah, H.N. , Turbulent blood flow in the ascending aorta of humans with normal and
diseased aortic valves, Circ. Res., 39, 58, 1976.

Mechanical Stresses in the Aortic Valve

Thubrikar, M. , Piepgrass, W.C. , Deck, J.D. , and Nolan, S.P. , Stresses of natural versus prosthetic aortic
valve leaflets in vivo, Ann. Thorac. Surg., 30, 230, 1980.
Yamada, H. , Strength of Biological Materials, Williams and Wilkins, Baltimore, 1970, 111.
Clark, R.E. , Stress-strain characteristics of fresh and frozen human aortic and mitral leaflets and chordae
tendinae: implications for clinical use, J. Thorac. Cardiovasc. Surg., 66, 202, 1973.
Missirlis, Y.F. and Chong, M. , Aortic valve mechanics. I. Material properties of natural porcine aortic valves,
J. Bioengng., 2, 287, 1978.
Rousseau, E.P.M. , Sauren, A.A.H.J. , van Hout, M.C. , and van Steenhoven, A.A. , Elastic and viscoelastic
material behaviour of fresh and glutaraldehyde-treated porcine aortic valve tissue, J. Biomech., 16, 339,
1983.
Thubrikar, M. , Piepgrass, W.C. , Bosher, L.P. , and Nolan, S.P. , The elastic modulus of canine aortic valve
leaflets in vivo and in vitro, Circ. Res., 47, 792, 1980.
Thubrikar, M.J. , Aouad, J. , and Nolan, S.P. , Comparison of the in vivo and in vitro mechanical properties of
aortic valve leaflets, J. Thorac. Cardiovasc. Surg., 92, 29, 1986.
Broom, N. and Christie, G.W. , The structure/function relationship of fresh and glutaraldehyde-fixed aortic
valve leaflets, in Cardiac Bioprostheses: Proc. 2nd Int. Symp., Cohn, L.H. and Gallucci, V. , Eds., Yorke, New
York, 1982, 476.
Sauren, A. A.H.J. , van Hout, M.C. , van Steenhoven, A.A. , Veldpaus, F.E. , and Janssen, J.D. , The
mechanical properties of porcine aortic valve tissues, J. Biomechanics, 16, 327, 1983.
Fung, Y.C. , Biomechanics: Mechanical Properties of Living Tissues, Springer-Verlag, New York, 1981.
Wright, J.E.C. and Ng, Y.L. , Elasticity of human aortic valve cusps, Cardiovasc. Res., 8, 384, 1974.
Driscol, T.E. and Eckstein, R.W. , Systolic pressure gradients across the aortic valve and in the ascending
aorta, Am. J. Physiol., 209, 557, 1965.
Gould, P.L. , Cataloglu, A. , Dhatt, G. , Chattopadhyay, A. , and Clark, R.E. , Stress analysis of the human
aortic valve, Comput. Struct., 3, 377, 1973.
Cataloglu, A. , Gould, P.L. , and Clark, R.E. , Refined stress analysis of human aortic heart valves, J. Eng.
Mech. Div. Proc. Am. Soc. Civil Eng., 102, 135, 1976.
Cataloglu, A. , Clark, R.E. , and Gould, P.L. , Stress analysis of aortic valve leaflets with smoothed
geometrical data, J. Biomech., 10, 153, 1977.
Thubrikar, M.J. , Nolan, S.P. , Aouad, J. , and Deck, J.D. , Stress sharing between the sinus and leaflets of
canine aortic valve, Ann. Thorac. Surg., 42, 434, 1986.
Deck, J.D. , Thubrikar, M.J. , Schneider, P.J. , and Nolan, S.P. , Structure, stress, and tissue repair in aortic
valve leaflets, Cardiovasc. Res., 22, 7, 1988.
Swanson, W.M. and Clark, R.E. , Motion and stresses in aortic valve leaflet during systole, Paper 72-
WA/BHF-5, presented at American Society of Mechanical Engineers, Biomechanical and Human Factors
Division, Winter Annual Meeting, New York, November 26 to 30, 1972.
Lim, K.O. and Boughner, D.R. , The low frequency dynamic viscoelastic properties of human aortic valve
tissue, Circ. Res., 39, 209, 1976.
Tan, A.J.K. and Holt, D.L. , The effects of sterilization and storage treatments on the stress-strain behavior of
aortic valve leaflets, Ann. Thorac. Surg., 22, 188, 1976.
Ng, Y.L. and Wright, J.E.C. , Effect of preservation on the elasticity of human aortic valve homografts, Thorax,
30, 266, 1975.

Echocardiography of the Aortic Valve

Gramiak, R. and Shah, P.M. , Echocardiography of the normal and diseased aortic valve, Radiology, 96, 1,
1970.
Hernberg, J. , Weiss, B. , and Keegan, A. , The ultrasonic recording of aortic valve motion, Radiology, 94,
361, 1970.
Gramiak, R. and Shah, P.M. , Echocardiography of the aortic root, Invest. Radiol., 3, 356, 1968.
Pinto, E.R. , Damani, P.M. , Sternberg, C.N. , and Liedtke, A.J. , Fine flutterings of the aortic valve as
demonstrated by aortic valve echocardiograms, Am. Heart J., 95, 807, 1978.
Hofmann, T. , Kasper, W. , Meinertz, T. , Spillner, G. , Schlosser, V. , and Just, H. , Am. J. Cardiol., 59, 330,
1987.
Goldberg, B.B. , Kotler, M.N. , Ziskin, M.C. , and Waxham, R.D. , Diagnostic Uses of Ultrasound, Grune &
Stratton, New York, 1975, 48.
Feigenbaum, H. , Ed., Echocardiography, Lea & Febiger, Philadelphia, 1981, 76.
De Maria, A.N. , Bommer, W. , Joye, J. , Lee, G. , Bauteller, J. , and Mason, D.T. , Value and limitations of
cross-sectional echocardiography of the aortic valve in the diagnosis and quantification of valvular aortic
stenosis, Circulation, 62, 304, 1980.
Godley, R.W. , Green, D. , Dillon, J.C. , Rogers, E.W. , Feigenbaum, H. , and Weyman, A.E. , Reliability of
two-dimensional echocardiography in assessing the severity of valvular aortic stenosis, Chest, 79, 657, 1981.
Pollick, C. , Pittman, M. , Filly, K. , Fitzgerald, P.J. , and Popp, R.L. , Mitral and aortic valve orifice area in
normal subjects and in patients with congestive cardiomyopathy: determination by two dimensional
echocardiography, Am. J. Cardiol., 49, 1191, 1982.
D’Cruz, I.A. , Echocardiographic Analysis: Differential Diagnosis of M-Mode and Two-Dimensional
Echographic Appearances, Macmillan, New York, 1983, 129.
Roberts, W.C. , The congenitally bicuspid aortic valve: a study of 85 autopsy cases, Am. J. Cardiol., 26, 72,
1970.
Nanda, N.C. , Gramiak, R. , Manning, J. , Mahoney, E.B. , Lipchik, E.O. , and DeWeese, J.A. ,
Echocardiographic recognition of the congenital bicuspid aortic valve, Circulation, 49, 870, 1974.
Weyman, A.E. , Feigenbaum, H. , Dillon, J.C. , and Chang, S. , Cross-sectional echocardiography in
assessing the severity of valvular aortic stenosis, Circulation, 52, 828, 1975.
Fowles, R.E. , Martin, R.P. , Abrams, J.M. , Schapira, J.N. , French, J.W. , and Popp, R.L. , Two-dimensional
echocardiographic features of bicuspid aortic valve, Chest, 75, 434, 1979.
Goldberg, B.B. , Kotler, M.N. , Ziskin, M.C. , and Waxham, R.D. , Diagnostic Uses of Ultrasound, Grune &
Stratton, New York, 1975, 23.
Richards, K.L. , Doppler echocardiographic quantification of stenotic valvular lesions, Echocardiography, 4,
289, 1987.
Zoghbi, W.A. , Echocardiographic and Doppler ultrasonic evaluation of valvular aortic stenosis,
Echocardiography, 5, 23, 1988.
Pearlman, A.S. and Otto, C.M. , Quantification of valvular regurgitation, Echocardiography, 4, 271, 1987.
Production of Aortic Valve Sound
Coleman, D.J. , On the origin of the second heart sound, Am. Heart J., 65, 237, 1963.
MacCanon, D.M. , Arevalo, F. , and Meyer, E.C. , Direct detection and timing of aortic valve closure, Circ.
Res., 14, 387, 1964.
Piemme, T.E. , Barnett, G.O. , and Dexter, L. , Relationship of heart sounds to acceleration of blood flow,
Circ. Res., 18, 303, 1966.
Van Bogaert, A. , Role of the valves in the genesis of normal heart sounds, Cardiologia, 52, 330, 1968.
Prakash, R. , Second heart sound: a phono-echocardiographic correlation in 20 cardiac patients, J. Am.
Geriatr. Soc., 26, 372, 1978.
Anastassiades, P.C. , Quinones, M.A. , Gaasch, W.H. , Adyanthaya, A.V. , Waggoner, A.D. , and Alexander,
J.K. , Aortic valve closure: echocardiographic, phonocardiographic, and hemodynamic assessment, Am.
Heart J., 91, 228, 1976.
Laniado, S. , Yellin, E. , Terdiman, R. , Meytes, I. , and Stadler, J. , Hemodynamic correlates of the normal
aortic valve echogram: a study of sound, flow, and motion, Circulation, 54, 729, 1976.
Sabbah, H.N. and Stein, P.D. , Investigation of the theory and mechanism of the origin of the second heart
sound, Circ. Res., 39, 874, 1976.
Sabbah, H.N. and Stein, P.D. , Relation of the second sound to diastolic vibration of the closed aortic valve,
Am. J. Physiol, 234, H696, 1978.
Stein, P.D. , Mathematical model of valve vibration, in A Physical and Physiological Basis for the
Interpretation of Cardiac Auscultation: Evaluations Based Primarily on the Second Sound and Ejection
Murmurs, Futura, Mount Kisco, NY, 1981, 20.
McDonald, D.A. , Blood Flow in Arteries, Williams & Wilkins, Baltimore, 1974, 146.
Yoganathan, A.P. , Gupta, R. , Corcoran, W.H. , Udwadia, F.E. , Sarma, R. , and Bing, R.J. , Use of the fast
Fourier transform in the frequency analysis of the second heart sound in normal man, Med. and Biol. Eng.,
14, 455, 1976.
Stein, P.D. , Sabbah, H.N. , Lakier, J.B. , and Goldstein, S. , Frequency spectrum of the aortic component of
the second heart sound in patients with normal valves, aortic stenosis and aortic porcine xenografts, Am. J.
Cardiol, 46, 48, 1980.
Stein, P.D. and Sabbah, H. , Intensity of the second heart sound: relation of physical, physiological and
anatomic factors to auscultatory evaluation, Henry Ford Hosp. Med. J., 28, 205, 1980.
Sabbah, H.N. , Khaja, F. , Anbe, D.T. , Folger, G.M. , and Stein, P.D. , Determinants of the amplitude of the
aortic component of the second heart sound in aortic stenosis, Am. J. Cardiol, 41, 830, 1978.
Mazumdar, J. and Woodard-Knight, D. , A mathematical study of semilunar valve vibration, J. Biomech., 17,
639, 1984.
Sikarskie, D.L. , Stein, P.D. , and Vable, M. , A mathematical model of aortic valve vibration, J. Biomech., 17,
831, 1984.
Lim, K.O. , Liew, Y.-C. , and Oh, C.H. , Analysis of mitral and aortic valve vibrations and their role in the
production of the first and second heart sounds, Phys. Med. Biol, 25, 727, 1980.
Blick, E.F. , Sabbah, H.N. , and Stein, P.D. , One-dimensional model of diastolic semilunar valve vibrations
productive of heart sounds, J. Biomech., 12, 223, 1979.
Stein, P.D. , Sabbah, H.N. , Lakier, J.B. , Magilligan, D.J. , and Goldstein, S. , Frequency of the first heart
sound in the assessment of stiffening of mitral bioprosthetic valves, Circulation, 63, 200, 1981.
Brais, M. , Durand, L.-G. , Blanchard, M. , de Guise, J. , Guardo, R. , and Keon, W.J. , Frequency analysis of
Ionescu-Shiley prosthetic closing sounds in patients with normally functioning prostheses, Med. Biol Eng.
Comput., 24, 637, 1986.
Cloutier, G. , Guardo, R. , and Durand, L.-G. , Spectral analysis of closing sounds produced by Ionescu-
Shiley bioprosthetic aortic heart valves. I. Optimal number of poles and zeros for parametric spectral analysis,
Med. Biol. Eng. Comput., 25, 487, 1987.
Cloutier, G. , Grenier, M.-C. , Guardo, R. , and Durand, L.-G. , Spectral analysis of closing sounds produced
by Ionescu-Shiley bioprosthetic aortic heart valves. II. Computer simulation of aortic closing sounds and
estimation of their truncation level and signal-to-noise ratio, Med. Biol. Eng. Comput., 25, 492, 1987.
Durand, L.-G. , Blanchard, M. , Sabbah, H.N. , Hamid, M.S. , Kemp, S.R. , and Stein, P.D. , A Bayes model
for automatic detection and quantification of bioprosthetic valve degeneration, Proc. 6th Int. Conf.
Mathematical Modelling, 1987, in press.
Diseases of the Aortic Valve
Roberts, W.C. and Elliott, L.P. , Lesions complicating the congenitally bicuspid aortic valve: anatomic and
radiographic features, Radiol. Clin. North Am., 6, 409, 1968.
Passik, C.S. , Ackermann, D.M. , Pluth, J.R. , and Edwards, W.D. , Temporal changes in the causes of aortic
stenosis: a surgical pathologic study of 646 cases, Mayo Clin. Proc., 62, 119, 1987.
Subramanian, R. , Olson, L.J. , and Edwards, W.D. , Surgical pathology of pure aortic stenosis: a study of
374 cases, Mayo Clin. Proc., 59, 683, 1984.
Thubrikar, M.J. , Aouad, J. , and Nolan, S.P. , Patterns of calcific deposits in operatively excised stenotic or
purely regurgitant aortic valves and their relation to mechanical stress, Am. J. Cardiol., 58, 304, 1986.
Roberts, W.C. , The congenitally bicuspid aortic valve: a study of 85 autopsy cases, Am. J. Cardiol., 26, 72,
1970.
Olson, L.J. , Subramanian, R. , and Edwards, W.D. , Surgical pathology of pure aortic insufficiency: a study of
225 cases, Mayo Clin. Proc., 59, 835, 1984.
Campbell, M. , Calcific aortic stenosis and congenital bicuspid aortic valves, Br. Heart J., 30, 606, 1968.
Hallgrimsson, J. and Tulinius, H. , Chronic non-rheumatic aortic valvular disease: a population study based
on autopsies, J. Chron. Dis., 32, 355, 1979.
Mills, P. , Leech, G. , Davies, M. , and Leatham, A. , The natural history of a non-stenotic bicuspid aortic
valve, Br. Heart J., 40, 951, 1978.
Waller, B.F. , Carter, J.B. , Williams, H.J. , Wang, K. , and Edwards, J.E. , Bicuspid aortic valve: comparison
of congenital and acquired types, Circulation, 48, 1140, 1973.
Fenoglio, J.J. , McAllister, H.A. , De Castro, C.M. , Davia, J.E. , and Cheitlin, M.D. , Congenital bicuspid aortic
valve after age 20, Am. J. Cardiol., 39, 164, 1977.
Moore, G.W. , Hutchins, G.M. , Brito, J.C. , and Kang, H. , Congenital malformations of the semilunar valves,
Hum. Pathol., 11, 367, 1980.
Milo, S. , Neufeld, H.A. , and Goor, D.A. , Incomplete commissure of the aortic valve, Thorax, 37, 636, 1982.
Edwards, J.E. , On the etiology of calcific aortic stenosis (editorial), Circulation, 25, 817, 1962.
Falcone, M.W. , Roberts, W.C. , Morrow, A.G. , and Perloff, J.K. , Congenital aortic stenosis resulting from a
unicommissural valve: clinical and anatomic features in twenty-one adult patients, Circulation, 44, 272, 1971.
Roberts, W.C. , Dangel, J.C. , and Bulkley, B.H. , Nonrheumatic valvular cardiac disease: a clinicopathologic
survey of 27 different conditions causing valvular dysfunction, Cardiovasc. Clin., 5, 333, 1973.
Iglesias, A. , Oliver, J. , Munoz, J.E. , and Nunez, L. , Quadricuspid aortic valve associated with fibromuscular
subaortic stenosis and aortic regurgitation treated by conservative surgery, Chest, 80, 327, 1981.
Luisi, V.S. , Pasque, A. , Verunelli, F. , Aliboni, M. , Urbano, U. , and Reginato, E. , Quadricuspid aortic valve,
J. Cardiovasc. Surg., 25, 252, 1984.
Vollebergh, F.E.M.G. and Becker, A.E. , Minor congenital variations of cusp size in tricuspid aortic valves:
possible link with isolated aortic stenosis, Br. Heart J., 39, 1006, 1977.
Silver, M.A. and Roberts, W.C. , Detailed anatomy of the normally functioning aortic valve in hearts of normal
and increased weight, Am. J. Cardiol., 55, 454, 1985.
Edwards, J.E. , The congenital bicuspid aortic valve, Circulation, 23, 485, 1961.
Sell, S. and Scully, R.E. , Aging changes in the aortic and mitral valves, Am. J. Pathol., 46, 345, 1965.
Kim, K.M. , Valigorsky, J.M. , Mergner, W.J. , Jones, R.T. , Pendergrass, R.F. , and Trump, B.F. , Aging
changes in the human aortic valve in relation to dystrophic calcification, Hum. Pathol., 7, 47, 1976.
Stein, P.D. , Sabbah, H.N. , and Pitha, J. , Continuing disease process of calcific aortic stenosis: role of
microthrombi and turbulent flow, Am. J. Cardiol., 39, 159, 1977.
Tala, P. , Salonen, I.S. , and Rissanen, K. , The patho-anatomical basis of aortic valve replacement: autopsy
observations of 100 unselected cases, Ann. Chir. Gynecol. Fenn., 57, 184, 1968.
Mönckeberg, J.G. , Der normale histologische Bau und die Sklerose der Aortenklappen, Virch. Arch. Pathol.
Anat., 176, 472, 1904.
Hultgren, H.N. , Calcific disease of the aortic valve, Arch. Pathol., 45, 694, 1948.
McMillan, J.B. and Lev, M. , The aging heart. II. The valves, J. Gerontol., 19, 1, 1964.
Angrist, A. , Aging heart valves and a unitary pathological hypothesis for sclerosis, J. Gerontol., 19, 135,
1964.
Replacement Cardiac Valves
Brewer, L.A. , Prosthetic Heart Valves, Charles C Thomas, Springfield, IL, 1969.
Morse, D. , Steiner, R.M. , and Fernandez, J. , Eds., Guide to Prosthetic Cardiac Valves, Springer-Verlag,
New York, 1985.
Schoen, F.J. , Cardiac valve prostheses: pathological and bioengineering considerations, J. Cardiac Surg., 2,
65, 1987.
Schoen, F.J. , Cardiac valve prostheses: review of clinical status and contemporary biomaterials issues, J.
Biomed. Mater. Res. Appl. Biomat., 21, 91, 1987.
Reul, H. , Giersiepen, M. , and Knott, E. , Laboratory testing of prosthetic heart valves, Eng. Med., 16, 67,
1987.
Wright, J.T.M. and Temple, L.J. , A flow visualization study of prosthetic aortic and mitral heart valves in a
model of the aorta and left heart, Eng. Med., 6, 31, 1977.
Thubrikar, M. , Skinner, J.R. , Aouad, J. , Finkelmeier, B.A. , and Nolan, S.P. , Analysis of the design and
dynamics of aortic bioprostheses in vivo, J. Thorac. Cardiovasc. Surg., 84, 282, 1982.
Lane, W.Z. and Ranganathan, V. , Autograft die for the production of aortic valves from fascia lata, Angiology,
21, 305, 1970.
Manothaya, C. , Vattanapat, S. , and Somabutr, C. , New technique for construction of tissue heart valves,
Thorax, 35, 611, 1980.
Clark, R.E. , Gould, P.L. , Swanson, W.M. , Kardos, J.L. , Karara, H.M. , Skelton, J. , and Butterworth, G.A.M.
, Design and fabrication of prosthetic leaflet heart valves, Biomat. Med. Dev. Artif. Org., 2, 379, 1974.
Liotta, D. , Bracco, D. , Ferrari, H. , Bertolozzi, E. , Pisanu, A. , and Donato, O. , Low profile bioprosthesis for
cardiac valve replacement: early clinical results, Cardiovascular Diseases, Bulletin of the Texas Heart
Institute, 4, 371, 1977.
Imamura, E. , Ishihara, S. , Ohteki, H. , Aomi, S. , and Koyanagi, H. , Open-position fixation of bioprostheses
for more physiological performance: fluoroscopic observations of leaflet movements in vivo, J. Thorac.
Cardiovasc. Surg., 88, 114, 1984.
Reis, R.L. , Hancock, W.D. , Yarbrough, J.W. , Glancy, D.L. , and Morrow, A.G. , The flexible stent: a new
concept in the fabrication of tissue heart valve prostheses, J. Thorac. Cardiovasc. Surg., 62, 683, 1971.
Ghista, D.N. , Toward an optimum prosthetic trileaflet aortic-valve design, Med. Biol. Eng., 14, 122, 1976.
Thubrikar, M.J. , Samanta, S. , and Nolan, S.P. , The principles of aortic valve design, Trans. Am. Soc. Artif.
Intern. Organs, submitted.
Cohn, L.H. and Gallucci, V. , Cardiac Bioprostheses: Proceedings of the Second International Symposium,
Yorke Medical Books, New York, 1982.
Gabbay, S. and Gabrol, C. , Eds., Calcification and Degeneration of Heart Valve Bioprostheses: Proceeding
of the First Scientific Meeting of the International Association for Cardiac Biological Implants, Dr. A. Ameur,
Communication Medicale, Paris, 1987.
Lawford, P.V. , Black, M.M. , Drury, P.J. , Roberts, K. , and Bilton, G. , The in vivo durability of bioprosthetic
heart valves — modes of failure observed in explanted valves, Eng. Med., 16, 95, 1987.
Thandroyen, F.T. , Whitton, I.N. , Pirie, D. , Rogers, M.A. , and Mitha, A.S. , Severe calcification of
glutaraldehyde-preserved porcine xenografts in children, Am. J. Cardiol., 45, 690, 1980.
Cipriano, P.R. , Billingham, M.E. , Oyer, P.E. , Kutsche, L.M. , and Stinson, E.B. , Calcification of porcine
prosthetic heart valves: a radiographic and light microscopic study, Circulation, 66, 1100, 1982.
Geha, A.S. , Hammond, G.L. , Laks, H. , Stansel, H.C. , and Glenn, W.W.L. , Factors affecting performance
and thromboembolism after porcine xenograft cardiac valve replacement, J. Thorac. Cardiovasc. Surg., 83,
377, 1982.
Cohn, L.H. , Allred, E.N. , Disesa, V.J. , Sawtelle, K. , Shemin, R.J. , and Collins, J.J. , Early and late risk of
aortic valve replacement. A 12-year concomitant comparison of the porcine bioprosthetic and tilting disc
prosthetic aortic valves, J. Thorac. Cardiovasc. Surg., 88, 695, 1984.
Cohn, L.H. , Allred, E.N. , Cohn, L.A. , Austin, J.C. , Sabik, J. , Disesa, V.J. , Shemin, R.J. , and Collins, J.J. ,
Early and late risk of mitral valve replacement. A 12-year concomitant comparison of the porcine bioprosthetic
and prosthetic disc mitral valves, J. Thorac. Cardiovasc. Surg., 90, 872, 1985.
Ferrans, V.J. , Boyce, S.W. , Billingham, M.E. , Jones, M. , Ishihara, T. , and Roberts, W.C. , Calcific deposits
in porcine bioprostheses: structure and pathogenesis, Am. J. Cardiol., 46, 721, 1980.
Riddle, J.M. , Jennings, J.J. , Stein, P.D. , and Magilligan, D.J., Jr. , A morphologic overview of the porcine
bioprosthetic valve — before and after its degeneration, Scanning Electron Microsc., I, 207, 1984.
Ishihara, T. , Ferrans, V.J. , Boyce, S.W. , Jones, M. , and Roberts, W.C. , Structure and classification of
cuspal tears and perforations in porcine bioprosthetic cardiac valves implanted in patients, Am. J. Cardiol.,
48, 665, 1981.
Salomon, N.W. , Copeland, J.G. , Goldman, S. , and Larson, D.F. , Unusual complication of the Hancock
porcine heterograft: strut compression in the aortic root, J. Thorac. Cardiovasc. Surg., 77, 294, 1979.
Borkon, A.M. , McIntosh, C.L. , Jones, M. , Roberts, W.C. , and Morrow, A.G. , Inward stent-post bending of a
porcine bioprosthesis in the mitral position: cause of bioprosthetic dysfunction, J. Thorac. Cardiovasc. Surg.,
83, 105, 1982.
Walley, V.M. and Keon, W.J. , Patterns of failure in Ionescu-Shiley bovine pericardial bioprosthetic valves, J.
Thorac. Cardiovasc. Surg., 93, 925, 1987.
Wheatley, D.J. , Fisher, J. , Reece, I.J. , Spyt, T. , and Breeze, P. , Primary tissue failure in pericardial heart
valves, J. Thorac. Cardiovasc. Surg., 94, 367, 1987.
Schoen, F.J. , Fernandez, J. , Gonzalez-Lavin, L. , and Cernaianu, A. , Causes of failure and pathologic
findings in surgically removed Ionescu-Shiley standard bovine pericardial heart valve bioprostheses:
emphasis on progressive structural deterioration, Circulation, 76, 618, 1987.
Barnhart, G.R. , Jones, M. , Ishihara, T. , Chavez, A.M. , Rose, D.M. , and Ferrans, V.J. , Bioprosthetic
valvular failure: clinical and pathological observations in an experimental animal model, J. Thorac.
Cardiovasc. Surg., 83, 618, 1982.
Thubrikar, M.J. , Deck, J.D. , Aouad, J. , and Nolan, S.P. , Role of mechanical stress in calcification of aortic
bioprosthetic valves, J. Thorac. Cardiovasc. Surg., 86, 115, 1983.
Thubrikar, M.J. , Nolan, S.P. , Deck, J.D. , Aouad, J. , and Levitt, L.C. , Intrinsic calcification of T6-processed
and control porcine and bovine bioprostheses in calves, Trans. Am. Soc. Artif. Intern. Organs, 29, 245, 1983.
Gorlin, R. and Gorlin, S.G. , Hydraulic formula for the calculation of the area of the stenotic mitral valve, other
cardiac valves and central circulating shunts, Am. Heart J., 41, 1, 1951.
Gabbay, S. , Bortolotti, U. , and Josif, M. , Mechanical factors influencing the durability of heart valve
pericardial bioprostheses, Trans. Am. Soc. Artif. Intern. Organs, 32, 282, 1986.
Clark, R.E. and Swanson, W.M. , In vitro durability of Hancock Model 242 porcine heart valve, J. Thorac.
Cardiovasc. Surg., 78, 277, 1979.
Lentz, D.J. , Pollock, E.M. , Olsen, D.B. , and Andrews, E.J. , Prevention of intrinsic calcification in porcine
and bovine xenograft materials, Trans. Am. Soc. Artif. Intern. Organs, 28, 494, 1982.
Thiene, G. , Laborde, F. , Valente, M. , Bical, O. , Talenti, E. , Bortolotti, U. , and Gallix, P. , Experimental
evaluation of porcine-valved conduits processed with a calcium-retarding agent (T6), J. Thorac. Cardiovasc.
Surg., 91, 215, 1986.
Golomb, G. , Dixon, M. , Smith, M.S. , Schoen, F.J. , and Levy, R.J. , Controlled-release drug delivery of
diphosphonates to inhibit bioprosthetic heart valve calcification: release rate modulation with silicone matrices
via drug solubility and membrane coating, J. Pharm. Sci., 76, 271, 1987.
Bodnar, E. , Olsen, E.G.J. , Florio, R. , and Dobrin, J. , Damage of porcine aortic valve tissue caused by the
surfactant sodiumdodecylsulphate, Thorac. Cardiovasc. Surgeon, 34, 82, 1986.
Broom, N.D. and Thomson, F.J. , Influence of fixation conditions on the performance of glutaraldehyde-
treated porcine aortic valves: towards a more scientific basis, Thorax, 34, 166, 1979.
Broom, N.D. , An “in vitro” study of mechanical fatigue in glutaraldehyde-treated porcine aortic valve tissue,
Biomaterials, 1, 3, 1980.
Trowbridge, E.A. and Crofts, C.E. , Pericardial heterografts: a method for leaflet mechanical property control,
Eng. Med., 16, 111, 1987.
Broom, N.D. , Fatigue-induced damage in glutaraldehyde-preserved heart valve tissue, J. Thorac.
Cardiovasc. Surg., 76, 202, 1978.
Thubrikar, M.J. , Skinner, J.R. , Eppink, R.T. , and Nolan, S.P. , Stress analysis of porcine bioprosthetic heart
valves in vivo , J. Biomed. Mater. Res., 16, 811, 1982.
Christie, G.W. and Medland, I.C. , A non-linear finite element stress analysis of bioprosthetic heart valves, in
Finite Elements in Biomechanics, Gallagher, R.H. , Simon, B.R. , Johnson, P.C. , and Gross, J.F. , Eds., John
Wiley & Sons, Chichester, 1982, chap. 9.
Sabbah, H.N. , Hamid, M.S. , and Stein, P.D. , Estimation of mechanical stresses on closed cusps of porcine
bioprosthetic valves: effects of stiffening, focal calcium and focal thinning, Am. J. Cardiol., 55, 1091, 1985.
Trowbridge, E.A. and Crofts, C.E. , Pericardial heterograft valves: an assessment of leaflet stresses and their
implications for heart valve design, J. Biomed. Eng., 9, 345, 1987.
Thubrikar, M. and Eppink, R.T. , A method for analysis of bending and shearing deformations in biological
tissue, J. Biomechanics, 15, 529, 1982.
Hudson, R.E.B. , Pathology of the human aortic valve homograft, Br. Heart J., 28, 291, 1966.
Barratt-Boyes, B.G. , Roche, A.H.G. , Subramanyan, R. , Pemberton, J.R. , and Whitlock, R.M.L. , Long-term
follow-up of patients with the antibiotic-sterilized aortic homograft valve inserted freehand in the aortic
position, Circulation, 75, 768, 1987.
Barratt-Boyes, B.G. and Roche, A.H.G. , A review of aortic valve homografts over a six and one-half year
period, Ann. Surg., 170, 483, 1969.
Barratt-Boyes, B.G. , Lowe, J.B. , Cole, D.S. , and Kelly, D.T. , Homograft valve replacement for aortic valve
disease, Thorax, 20, 495, 1965.
Brock, L. , Long-term degenerative changes in aortic segment homografts, with particular reference to
calcification, Thorax, 23, 249, 1968.
Savage, P.E.A. , Clayton Jones, D.G. , Thompson, A.E. , and Ross, D.N. , The fate of aortic valve
homografts, Br. J. Surg., 59, 231, 1972.
Ross, D.N. , Homograft replacement of the aortic valve, J. Cardiovasc. Surg. (Torino), Suppl., 89, 1965.
Thompson, R. , Yacoub, M.H. , Ahmed, M. , Somerville, W. , and Towers, M. , The use of “fresh” unstented
homograft valves for replacement of the aortic valve: analysis of 8 years’ experience, J. Thorac. Cardiovasc.
Surg., 79, 896, 1980.
Anderson, E.T. and Hancock, E.W. , Long-term follow-up of aortic valve replacement with the fresh aortic
homograft, J. Thorac. Cardiovasc. Surg., 72, 150, 1976.
Fishbein, M.C. , Levy, R.J. , Ferrans, V.J. , Dearden, L.C. , Nashef, A. , Goodman, A.P. , and Carpentier, A. ,
Calcification of cardiac valve bioprostheses: biochemical, histologic, and ultrastructural observations in a
subcutaneous implantation model system, J. Thorac. Cardiovasc. Surg., 83, 602, 1982.
Spray, T.L. and Roberts, W.C. , Structural changes in porcine xenografts used as substitute cardiac valves:
gross and histologic observations in 51 glutaraldehyde-preserved Hancock valves in 41 patients, Am. J.
Cardiol., 40, 319, 1977.
Ashraf, M. and Bloor, C.M. , Structural alterations of the porcine heterograft after various durations of
implantation, Am. J. Cardiol., 41, 1185, 1978.
Valente, M. , Bortolotti, U. , and Thiene, G. , Ultrastructural substrates of dystrophic calcification in porcine
bioprosthetic valve failure, Am. J. Pathol., 119, 12, 1985.
Nistal, F. , Garcia-Satue, E. , Artinano, E. , Duran, C.M.G. , and Gallo, I. , Comparative study of primary
tissue valve failure between Ionescu-Shiley pericardial and Hancock porcine valves in the aortic position, Am.
J. Cardiol., 57, 161, 1986.
Trowbridge, E.A. , Lawford, P.V. , Crofts, C.E. , and Roberts, K.M. , Pericardial heterografts: why do these
valves fail?, J. Thorac. Cardiovasc. Surg., 95, 577, 1988.
Borkon, A.M. , McIntosh, C.L. , Jones, M. , Lipson, L.C. , Kent, K.M. , and Morrow, A.G. , Hemodynamic
function of the Hancock standard orifice aortic valve bioprosthesis, J. Thorac. Cardiovasc. Surg., 82, 601,
1981.
Chaitman, B.R. , Bonan, R. , Lepage, G. , Tubau, J.F. , David, P.-R. , Dyrda, I. , and Grondin, C.M. ,
Hemodynamic evaluation of the Carpentier-Edwards porcine xenograft, Circulation, 60, 1170, 1979.
Yoganathan, A.P. , Woo, Y.-R. , Sung, H.-W. , Williams, F.P. , Franch, R.H. , and Jones, M. , In vitro
hemodynamic characteristics of tissue bioprostheses in the aortic position, J. Thorac. Cardiovasc. Surg., 92,
198, 1986.
De Biasi, S. , Pilotto, F. , and Pozzoni, F. , The glutaraldehyde-treated porcine aortic valve. A study of the
leaflets’ mechanical properties, Int. J. Artif. Organs, 3, 271, 1980.
Thomson, F.J. and Barratt-Boyes, B.G. , The glutaraldehyde-treated heterograft valve: some engineering
observations, J. Thorac. Cardiovasc. Surg., 74, 317, 1977.
Pohlner, P.G. , Thomson, F.J. , Hjelms, E. , and Barratt-Boyes, B.G. , Experimental evaluation of arotic
homograft valves mounted on flexible support frames and comparison with glutaraldehyde-treated porcine
valves, J. Thorac. Cardiovasc. Surg., 77, 287, 1979.
Mohri, H. , Hessel, E.A., II , Nelson, R.J. , Anderson, H.N. , Dillard, D.H. , and Merendino, K.A. , Design and
durability test of Silastic trileaflet aortic valve prostheses, J. Thorac. Cardiovasc. Surg., 65, 576, 1973.
D’Alessandro, A.A. , Construction of a new aortic valve: a new procedure and a preliminary report, Vasc.
Surg., 4, 151, 1970.