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GaetanoThiene· CristinaBasso·
StefaniaRizzo· MilaDellaBarbera·
MarialuisaValente·
UbertoBortolottiEditors
Pathology ofCardiac
Valve Disease
Surgical and Interventional Anatomy
123
Pathology of Cardiac Valve Disease
Gaetano Thiene • Cristina Basso
Stefania Rizzo • Mila DellaBarbera
Marialuisa Valente • Uberto Bortolotti
Editors
Pathology of Cardiac Valve
Disease
Surgical andInterventional Anatomy
Editors
Gaetano Thiene
Istituto di Anatomia Patologica
University of Padua
PADOVA, Padova, Italy
Stefania Rizzo
Cardiovascular Pathology, Department of Cardiac
Thoracic and Vascular Sciences
and Public. Health
University of Padua
Padova, Padova, Italy
Cristina Basso
Cardiovascular Pathology, Department of Cardiac
Thoracic and Vascular Sciences
and Public. Health
University of Padua
Padova, Padova, Italy
Mila DellaBarbera
Cardiac-Thoracic-Vasc. Sc. and P.Health
AOU University of Padua Medical School
Padova, Italy
Marialuisa Valente
Istituto di Anatomia Patologica
University of Padua
PADOVA, Padova, Italy
Uberto Bortolotti
Cardio-Thoracic and Vascular Department
Cardiac Surgery Unit
University of Pisa
Padova, Padova, Italy
ISBN 978-3-031-35497-7 ISBN 978-3-031-35498-4 (eBook)
https://doi.org/10.1007/978-3-031-35498-4
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or
part of the material is concerned, specically the rights of translation, reprinting, reuse of illustrations, recitation,
broadcasting, reproduction on microlms or in any other physical way, and transmission or information storage and
retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter
developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not
imply, even in the absence of a specic statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed
to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty,
expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been
made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional afliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
Foreword
Pathology of cardiac native and prosthetic valves.
I rst met Gaetano Thiene and Uberto Bortolotti in 1981 at the National Heart, Lung, and
Blood Institute (NIH) at Bethesda, where I was a fellow. Gaetano and Uberto were visiting
speakers. Gaetano and I were involved in the establishment of the Society for Cardiovascular
Pathology. We also shared an interest in cardiovascular prosthetic devices.
Gaetano Thiene, an accomplished cardiovascular pathologist, has spent his career teaching
pathology to generations of students and doing research at the University of Padua. He is now
Professor Emeritus at the University of Padua, Italy, with numerous scientic publications on
cardiovascular pathology, as well as book chapters and books to his credit. One of Gaetano
“seminal” papers was on arrhythmogenic right ventricular dysplasia (ARVD, now termed
arrhythmogenic cardiomyopathy), following a review of autopsied cases of sudden death in the
young. He is a founder of the European Association of Cardiovascular Pathology, and his inuence on the teaching and practice of cardiovascular pathology has been very impressive.
Uberto Bartolotti is a seasoned cardiovascular surgeon and colleague of Dr. Thiene. He has
numerous scientic publications and book chapters to his credit. He is now a retired Full
Professor of Cardiovascular Surgery at the University of Pisa, Italy.
They are both outstanding teachers, clinicians, and researchers.
Pathology, as in any part of Medicine, remains as much a science as an art. Like good wine, it
needs years of experience to mature and acquire its unique qualities. It is a pleasure to see this
book, a compilation of numerous years of expertise in the management of valvular heart disease.
This book, an atlas of valvular heart disease, native and prosthetic, shows its “maturity” in the
concise text and high-quality images. With the signicant changes in interventional management
of heart valve disease in the last decade, this book, with its section on trans-catheter heart valve
technologies, is a timely atlas and will likely be “one of its kind” for years to come.
The authors give a brief historical overview of the pathology of native valve diseases, the
development of prosthetic heart valves, followed by native and prosthetic valve pathology in a
concise and well-illustrated manner. Images of failed transcatheter aortic valve implantation
valves are likely to be especially valuable since there is little published about the pathology of
these devices. As one would expect, there are always some things “more” that could be added
to the atlas and this would include a more consistent approach to each valve, language that is
easier to understand, and the pathology of native valve repair (a niche area, but nonetheless one
with good clinical results).
v
vi
Cardiovascular pathology is a niche area, with a small number of practitioners worldwide.
This atlas will be a resource for many who need to report the pathology of native and prosthetic
valve disease. The concise format and the excellent quality of the illustrations suggest that the
book will be well received by residents, fellows, pathologists, cardiologists, and cardiovascular surgeons as a good reference and a great addition to institutional and personal libraries.
JagdishButany
Professor Emeritus, Faculty of Medicine
University of Toronto
Toronto, ON, Canada
Foreword
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Gaetano Thiene and Uberto Bortolotti
2 Story Telling of Prosthetic Cardiac Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Uberto Bortolotti and Gaetano Thiene
3 Anatomy of Native Heart Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Gaetano Thiene and Stefania Rizzo
4 Non Infections Pathology of Native Heart Valves . . . . . . . . . . . . . . . . . . . . . . . . . . 31
Cristina Basso and Gaetano Thiene
5 Congenital Anomalies of the Cardiac Valves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Carla Frescura and Gaetano Thiene
6 Infective Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Gaetano Thiene, Cristina Basso, and Uberto Bortolotti
7 Pathology of Mechanical Prosthetic Cardiac Valves . . . . . . . . . . . . . . . . . . . . . . . . 105
Uberto Bortolotti, Mila Della Barbera, Tomaso Bottio, and Gaetano Thiene
8 Pathology of Biological Prosthetic Cardiac Valves . . . . . . . . . . . . . . . . . . . . . . . . . 117
Gaetano Thiene, Mila Della Barbera, Aldo Milano, Stefania Rizzo, Uberto
Bortolotti, and Marialuisa Valente
9 Anticalcification Strategies to Increase Bioprosthetic Valve Durability . . . . . . . . 153
Marialuisa Valente, Mila della Barbera, Uberto Bortolotti, and Gaetano Thiene
vii
Introduction
GaetanoThiene andUbertoBortolotti
1
Until the late 1950s, heart valve diseases could be treated
only by closed-chest procedures, such as mitral valve commissurotomy or dilatation of stenotic pulmonary valves.
Despite satisfactory results, such operations were palliative
with only temporary benet. It was in 1960, by replacing the
mitral and aortic diseased valves with mechanical prostheses, thanks to the milestone operations performed by Nina
Braunwald, Albert Starr and Dwight E. Harken, that the
prognosis of patients affected by deadly valvular diseases
changed dramatically.
Within years, prosthetic valve replacement has progressively become an almost routine operation with excellent
early and long-term results. This has been certainly due also
to denite improvements in patient selection, intraoperative
management and postoperative care, which have occurred
during various decades. However, a crucial role has been
undoubtedly played by the tremendous technical progress
which has been achieved in the manufacture of cardiac valve
substitutes. With the initial prosthetic models, cardiac surgery pioneers have demonstrated their talent but also their
ingenuity. However, it was also evident that a still very long
and winding road would have been expected to obtain the
ideal device to be safely used in any kind of patient and
native pathology.
It was soon realized that mechanical prostheses were
associated with thrombotic, thromboembolic and hemorrhagic complications related to the often incorrect use and
management of life-long anticoagulants, while bioprosthetic
valves had the major drawback in a limited structural durability. The various causes of prosthetic valve failure were
G. Thiene (*)
Department of Cardiac, Thoracic, Vascular Sciences and Public
Health, University of Padua Medical School, and Cardiovascular
Pathology Unit, University Hospital of Padua, Padua, Italy
e-mail: gaetano.thiene@unipd.it
U. Bortolotti
Section of Cardiac Surgery, Cardio-thoracic and Vascular
Department, University Hospital of Pisa, Pisa, Italy
e-mail: uberto.bortolotti@med.unipi.it
clearly identied by a continuous research in this eld, with
the results shared with the scientic community through
numerous reports. Accordingly, it was possible to precisely
highlight the typical modes of failure of each specic device,
introduced in the market and made clinically available, either
mechanical or biological. This information has been of pivotal importance for the industry, since each involved company started to modify their early models based upon the
ndings observed and provided by clinicians and pathologists. This allowed to introduce important innovations in the
prosthesis manufacturing process and to eliminate structural
weakness, to increase biocompatibility, to minimize thrombogenicity of mechanical prostheses, and to improve hemodynamic performance, favoring ease of implantation and
extending durability for biological counterparts. Owing to
the great progress in prosthetic technology, after over
60years from the rst implant of a caged-ball mechanical
prosthesis and more than 50 years of a stented porcine bioprosthesis, we can say that a new generation of extremely
reliable and effective cardiac valve substitutes is now available. Despite this, it must be also recognized that the ten
commandments for what should be considered the ideal
prosthetic valve, devised by Dwight E.Harken many years
Table 1.1 The ten commandments for the ideal prosthetic valve
1. It must not propagate emboli
2. It must be chemically inert and not damage blood elements
3. It must offer no resistance to physiological ows
4. It must close promptly (less than 0.05second)
5. It must remain closed during the appropriate phase of the
cardiac cycle
6. It must have lasting physical and geometric features
7. It must be inserted in a physiological site (generally the normal
anatomic site)
8. It must be capable of permanent xation
9. It must not annoy the patient
10. It must be technically practical to insert
a
as originally dened by DE Harken
a
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
G. Thiene et al. (eds.), Pathology of Cardiac Valve Disease, https://doi.org/10.1007/978-3-031-35498-4_1
1
2
G. Thiene and U. Bortolotti
ago (Table1.1), are not yet totally fullled, witnessing that
probably there is still considerable research to be carried out
in the eld of prosthetic heart valves.
The present book, in the form of an illustrated text atlas
on the surgical anatomy and pathology of native and prosthetic heart valves, appears timely not only historically but
also of practical utility for all involved in this eld. The aim
of this book is to provide the reader with clear images of the
valve anatomy and pathology, including views from a cardiac surgeon’s perspective and pictures of most heart prosthetic models and their typical mode of failure.
All the materials included in this publication derived from
the collection of the Unit of Cardiovascular Pathology of the
University of Padua Medical School. The huge amount of
specimens gathered through the years and shared here will
help to demonstrate the importance of this contribution to the
progress in mechanical and bioprosthetic technology and to
the improvement in the care of prosthetic heart valve recipients. In the era of rapid and increasingly advancing trans-
catheter procedures, the present overview will also help to
understand the role of surgical valve replacement that with
the current available prosthetic models certainly cannot be
considered a yet outdated procedure.
Further Reading
Bortolotti U, Milano AD, Valente M, Thiene G. The stented porcine
bioprosthesis. A 50-year journey through hopes and realities. Ann
Thorac Surg. 2019;108:304–8.
De Martino A, Milano AD, Thiene G, Bortolotti U.Diamond anniver-
sary of mechanical heart valve prostheses. A tale of cages, balls and
discs. Ann Thorac Surg. 2020;110:1427–33.
De Martino A, Milano AD, Thiene G, Della Barbera M, Bortolotti
U.The caged-ball prosthesis 60 years later. Historical review of a
cardiac surgery milestone. Texas Heart Inst J. 2022;49:e207267.
Harken DE.Heart valves: ten commandments and still counting. Ann
Thorac Surg. 1989;48: (3 Suppl): S18-9:S18.
Lefrak EA, Starr A, editors. Cardiac valve prostheses. New York:
Appleton-Century-Crofts; 1979.
Story Telling ofProsthetic Cardiac
Valves
UbertoBortolotti andGaetanoThiene
2
The history of cardiac prosthetic valves starts in September
1952 when Charles A.Hufnagel implanted, at Georgetown
University, in Washington, DC, USA, the rst cardiac prosthesis, a ball valve made of methyl metachrylate, into the
descending aorta in a patient with aortic valve incompetence.
Unavailability at that time of the cardiopulmonary bypass
forced this unusual application which, however, had very
limited clinical benets. Mitral valve replacement had been
attempted in July 1955 by Judson Chesterman in Shefeld,
UK, using a prosthesis made of Perspex®, an acrylic material, which worked on the principles of a car engine valve.
The patient survived 14h and died because of sudden prosthetic failure. In March 1960, 8years from Hufnagel’s operation, Dwight E. Harken at the Harvard Medical School in
Boston, MA, USA, performed the rst orthotopic implantation of a caged-ball prosthesis in subcoronary position for
aortic stenosis, while 1 day later, Nina Braunwald, at the
National Institutes of Health, in Bethesda, MD, USA,
replaced for the rst time an incompetent mitral valve using
a prosthesis made from two leaets of polyurethane connected to the papillary muscles by strips of Teon; this prosthesis was implanted in a 44-year-old woman with mitral
regurgitation who survived the operation but died 4months
later, most likely for arrhythmia. Albert Starr in Portland,
OR, USA, is credited for the rst successful mitral valve
replacement performed with a caged-ball prosthesis in
September 1960in a patient with mitral stenosis. Such operations started the modern era of prosthetic valve replacement, and during the following decades, a wide variety of
U. Bortolotti (*)
Section of Cardiac Surgery, Cardio-thoracic and Vascular
Department, University Hospital of Pisa, Pisa, Italy
e-mail: uberto.bortolotti@med.unipi.it
G. Thiene
Department of Cardiac, Thoracic, Vascular Sciences and Public
Health, University of Padua Medical School, and Cardiovascular
Pathology Unit, University Hospital of Padua, Padua, Italy
e-mail: gaetano.thiene@unipd.it
mechanical prostheses became available with signicant
improvements in materials, structural design, shapes, and
hemodynamic concepts.
Major concerns with the use of mechanical devices, represented by anticoagulant-related complications such as
thromboembolism and hemorrhages, led to conceive biological alternatives for valve replacement which would eliminate
or minimize the burden and risks of chronic anticoagulation.
The rst heterologous bioprosthesis was implanted in Paris
by Binet in 1965 who employed a porcine aortic valve
inserted with the free-hand technique to replace a diseased
aortic valve. Subsequently, a stent was added to the porcine
valve to avoid tissue ingrowth, and glutaraldehyde was used
for tissue xation to stabilize the collagen cross-links, reduce
tissue antigenicity, and provide sterilization of the heterograft. These innovations represented the beginning of the
bioprosthetic era during which failures and successes have
been witnessed by a multitude of clinical and pathological
reports. Currently, due the widespread development of valve
repair techniques, the use of prosthetic valves has been conned to specic conditions. Due to the increasing age of the
population referred for surgical valve replacement, employment of mechanical devices is extremely limited in favor of
tissue valves, while expanding indications for transcatheter
aortic valve implantation has led to development of a further
generation of bioprostheses to be implanted with less invasive methods.
A wide variety of cardiac valve substitutes has been introduced clinically in the last 60years. Mechanical prostheses
have undergone most signicant improvements not only in
design but also in the use of different materials to obtain
devices resistant to mechanical stress and structural wear.
Conversely, in biological prosthesis manufacture, major
modications have involved tissue selection, methods of
xation, and the use of various anticalcication treatments,
while design variations have played an important role as
well. The valve prosthesis portfolio has recently been implemented by the manufacture of sutureless bioprostheses made
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
G. Thiene et al. (eds.), Pathology of Cardiac Valve Disease, https://doi.org/10.1007/978-3-031-35498-4_2
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