Table Of ContentHANDBOOK OF PATHOLOGY AND
PATHOPHYSIOLOGY OF CARDIOVASCULAR DISEASE
Developments in Cardiovascular Medicine
214. P. A. Doevendans, R.S. Reneman and M. Van Bilsen (eds): Cardiovascular Specific
Gene Expression. 1999 ISBN:0-7923-5633-0
215. G. Pons-Lladó, F. Carreras, X. Borrás, Subirana and L.J. Jiménez-Borreguero (eds.):
Atlas of Practical Cardiac Applications of MRI. 1999 ISBN: 0-7923-5636-5
216. L.W. Klein, J.E. Calvin, Resource Utilization in Cardiac Disease. 1999.
ISBN:0-7923-8509-8
217. R. Gorlin, G. Dangas, P. K. Toutouzas, M.M Konstadoulakis, Contemporary
Concepts in Cardiology, Pathophysiology and Clinical Management. 1999
ISBN:0-7923-8514-4
218. S. Gupta, J. Camm (eds.): Chronic Infection, Chlamydia and Coronary Heart
Disease. 1999. ISBN:0-7923-5797-3
219. M. Rajskina: Ventricular Fibrillation in Sudden Coronary Death. 1999.
ISBN:0-7923-8570-5
220. Z. Abedin, R. Conner: Interpretation ofCardiacArrhythmias: SelfAssessment
Approach. 1999. ISBN:0-7923-8576-4
221. J. E. Lock, J.F. Keane, S. B. Perry: Diagnostic and Interventional Catheterization
In Congenital Heart Disease. 2000. ISBN:0-7923-8597-7
222. J.S. Steinberg: Atrial Fibrillation after Cardiac Surgery. 2000.
ISBN:0-7923-8655-8
223. E.E. van der Wall, A. van der Laarse, B.M. Pluim, A.V.G. Bruschke: Left
Ventricular Hypertrophy: Physiology versus Pathology. 2000
ISBN:0-7923-6038-9
224. J.F. Keaney, Jr. (ed.): Oxidative Stress and Vascular Disease. 2000.
ISBN: 0-7923-8678-7
228. B.E. Jaski: Basicsof HeartFailure. 2000 ISBN:0-7923-7786-9
229. H.H. Osterhues, V. Hombach, A.J. Moss (eds.): Advances in Non-Invasive
Electrocardiographic Monitoring Techniques. 2000. ISBN: 0-7923-6214-4
230. K. Robinson (ed.): Homocysteine and Vascular Disease. 2000
ISBN: 0-7923-6248-9
231. C.I. Berul, J.A. Towbin (eds.): Molecular Genetics of Cardiac Electrophysiology.
2000. ISBN:0-7923-7829-6
232. A. Bayés de Luna, F. Furlanello, B.J. Maron and D.P. Zipes (eds.):
Arrhythmias and Sudden Death in Athletes. 2000 ISBN: 0-7923-6337-X
233. J-C. Tardif and M.G. Bourassa (eds): Antioxidants and Cardiovascular Disease.
2000. ISBN: 0-7923-7829-6
234. J. Candell-Riera, J. Castell-Conesa, S. Aguadé Bruiz (eds): Myocardium at
Risk and Viable Myocardium Evaluation by SPET. 2000.ISBN: 0-7923-6724-3
235. M.H. Ellestad and E. Amsterdam (eds): Exercise Testing:New Concepts forthe
New Century. 2001. ISBN: 0-7923-7378-2
236. Douglas L. Mann (ed.): TheRoleof InflammatoryMediators in theFailing
Heart. 2001 ISBN: 0-7923-7381-2
237. Donald M. Bers (ed.): Excitation-Contraction Coupling and Cardiac
Contractile Force, Second Edition. 2001 ISBN: 0-7923-7157-7
238. Brian D. Hoit, Richard A. Walsh (eds.): Cardiovascular Physiology in the
Genetically Engineered Mouse, Second Edition. 2001 ISBN 0-7923-7536-X
239. P.A. Doevendans, A.A.M. Wilde (eds.): CardiovascularGenetics for Clinicians.
2001 ISBN 1-4020-0097-9
240. S.M. Factor, M.A. Lamberti-Abadi, J. Abadi, (eds.): Handbook of Pathology and
Pathophysiology of Cardiovascular Disease. 2001 ISBN 0-7923-7542-4
Previous volumes are still available
HANDBOOK OF PATHOLOGY AND
PATHOPHYSIOLOGY OF CARDIOVASCULAR
DISEASE
by
STEPHEN M. FACTOR, MD, FCAP, ACC
Professor of Pathology and Medicine
Albert Einstein College of Medicine
Bronx, New York
MARIA A. LAMBERTI – ABADI, MD
Assistant Professor of Pathology
Albert Einstein College of Medicine
Bronx, New York
and
JACOBO ABADI, MD
Assistant Professor of Pediatrics
Albert Einstein College of Medicine
Bronx, New York
KLUWER ACADEMIC PUBLISHERS
NEW YORK, BOSTON, DORDRECHT, LONDON, MOSCOW
eBookISBN: 0-306-47575-8
Print ISBN: 0-7923-7542-4
©2002 Kluwer Academic Publishers
NewYork, Boston, Dordrecht, London, Moscow
Print ©2002 Kluwer Academic Publishers
Dordrecht
All rights reserved
No part of this eBook maybe reproducedor transmitted inanyform or byanymeans,electronic,
mechanical, recording, or otherwise, without written consent from the Publisher
Created in the United States of America
Visit Kluwer Online at: http://kluweronline.com
and Kluwer's eBookstore at: http://ebooks.kluweronline.com
To my darling wife, and my lovely children with deepest appreciation for
all your help and encouragement along the way. To my parents, for
making me what I am. And, of course, with love to Raja. SMF
With love to my husband Yaco, our children Daniela, Adriana and
David, my mom Renee, my brother Victor, and especially to my dad Jose
A. (Cucho) Lamberti, MD, whose memory is a driving force in my life.
MA
To my wife Lala and our kids, with all my HEART. You are the light of
my life. To my parents, sister, and grandmother Sara, with love. JA
TABLE OF CONTENTS
Preface viii
1. Practical Cardiac Anatomy 1
2. Atherosclerotic HeartDisease andIschemia 19
3. Diabetes andthe Heart 67
4. Cardiomyopathies 75
Hypertrophic
Dilated
Endocrinopathies
Alcoholic –Nutritional Deficiencies
Human ImmunodeficiencyVirusInfection
5. Valvulopathies 119
Rheumatic Heart Disease
Mitral Valve Prolapse
6. Congenital Heart Disease 137
Tetralogy ofFallot
Turner’s Syndrome
PatentDuctusArteriosus
7. Endocarditis 171
8. Myocarditis 191
9. Cardiac Tumors 203
10. The Pericardium 221
11. Aortic Aneurysms 229
12. CollagenVascularDiseasesandVasculitis: 241
Syphilis
Scleroderma
Systemic Lupus Erythematosus
Takayasu’s disease
Kawasaki’s disease
13. Medicine, LawandtheHeart 281
Appendix 299
Index 305
PREFACE
Autopsy derives from the greek word autopsia, which means act of
seeing with one’s own eyes. It remains the most objective and accurate
method to understand human.disease. Unfortunately, the volume of autopsies
in teaching hospitals has decreased dramatically over the past years. The
crucial factors that account for this are the recent progress and development of
new technologies, especially in diagnostic imaging, immunology, cell biology
and genetics. Additionally, the perpetual fear of legal liability by physicians
accounts for its further decline. Consequently, physicians and medical
students are engaged in fewer autopsies and are not reaping the rich
educational rewards that accompany these examinations. The purpose of the
autopsy is not only to establish the cause of death, but also to determine the
nature and course of the disease process. Our goal with this book is to
emphasize the importance of the post-mortem exam and the correlation
between pathologic material and clinical data by analyzing actual cases with
problem-based methodology. The focus of this handbook is on cardiovascular
disease, and when appropriate, other disease categories are included if they
have an impact on cardiovascular function.
The approach is more than the usual clinico-pathological correlation.
Rather, we attempt to present the material from the perspective of the autopsy
table. We use the clinical data as the initial framework and the autopsy
findings to develop a true understanding of the disease and the associated
pathophysiology of the condition. This approach is similar to the “gross”
autopsy conferences that have been carried out at our institution for over 30
years. The format of the case presentation is logical and uniform with
emphasis in teaching current medical concepts. Relevant clinical information
is correlated and evaluated in the context of the macroscopic and microscopic
findings obtained in the post-mortem exam. All cases are followed by a
comprehensive discussion and review of the disease and pertinent literature is
cited. We use extensive photographic material to illustrate each case and
facilitate learning.
We address the new issue of legal liability by presenting cases that
have medico-legal implications. A thorough discussion on the impact of
significant discrepancies between the autopsy findings and clinical diagnoses
is also included. This is particularly important in an era that demands quality
assurance and performance improvement from the medical professionals.
Scientific methodology and common sense are still essential despite
the forever growing knowledge of the medical sciences. Hopefully, with this
book, we will succeed in guiding physicians and medical students in their
continuous search for answers.
Chapter 1
PRACTICAL CARDIAC ANATOMY:
FROM A TO Z
Introduction
It may represent a bias ofthe authors, but it appears to be a truism to
state that the heart is the most complex anatomical structure in the body. Yes,
the brain has an intricate spatial and electrical anatomy with numerous nuclei
and interconnections, but it does not approach the complexity of the heart
anatomically or physiologically. No organ other than the heart is divided into
pumping chambers dependent on blood flow moving between two separate
circulatory circuits, with the timing ofblood movement within the chambers
occurring within fractions ofa second. This movement must be coordinated
by a neural network (e.g. conduction system), heart valves, vascular supply,
connective tissue and muscle cells. The heart is dependent on maintaining its
own nutrition, while at the same time supplying oxygenated blood to the
entire body. During the process ofpumping, chamber contraction affects the
supply of blood to the tissue performing the pumping, sometimes with
adverse consequences. There must be an adequate flow ofoxygenated blood
to the heart cells, because they have very high metabolic requirements.
Although myocytes are organized as individual cells and do not form a
syncytium, they must ‘talk’ to each other electrically and functionally. The
cells must each contract, but this contraction must then be coordinated so that
groups and layers of cells are shortening sequentially within a very short
period of time. Otherwise, this would lead to hypokinesia (decreased
contraction), dyskinesia (abnormal contraction), or akinesia (absence of
contraction).
Many books have been written on cardiac anatomy, both descriptive
and illustrated. Detailed descriptions are available ofthe complex structural
and functional anatomy ofthe heart; but most ofsuch works do not provide
adequate explanations for acquired pathophysiology or contractile
dysfunction. The rationale for this book is different: we are attempting to
correlate actual case material with clinically relevant findings, and to show
how clinical manifestations, pathophysiology and pathology interact to
produce disease. Furthermore, we want to show how there is a certain logic
and analytical process that goes into each case, if one understands clinical
findings and pathology. Our goal in this book is not to re-teach cardiac
anatomy. Those who are interested or stimulated to do so can find any
number ofadequate books and atlases on the subject. We want to provide a
brief outline of some basic features of cardiac anatomy, and by doing so,
make pathophysiology and disease manifestations meaningful.
The following provides an alphabetical functional anatomical
glossary. It is not proposed as a complete list, but one that illustrates the
principle that at least some cardiovascular diseases and their complications
are determined by cardiac anatomy and structure-function relationships.
Annulus
The fibrous ring that supports each of the 4 cardiac valves. The
annulus for the tricuspid, mitral, and aortic valves is virtually a continuous
structure arranged like a pretzel. The pulmonic valve annulus is somewhat
separate from the other 3 (it arises from distinctly independent embryologic
tissue, e.g. bulbus cordis). The valve base inserts into the annulus with inter-
digitating connective tissue fibers. Infection ofthe valve tissue (endocarditis)
can affect these connections thereby causing leaflet or cuspal dehiscence, or it
can lead to an infection ofthe annulus itself(e.g. valve ring abscess). The
proximity of the annulae of the 3 valves means that infection can spread
readily from one to the other. The annulus also anchors the base ofthe heart
through connective tissue attachment fibers that extend into the muscle of the
ventricle. Sections ofthe base ofthe heart just below the annulus typically
reveal fibrous tissue; however, this should not be interpreted as pathological
scar since it represents normal anatomy. Dilatation ofthe ventricular or atrial
chambers can stretch the annulae, most likely through side to side slippage of
the connective tissue fibers. The dilatation may pull the valve base away
from the center channel through which blood flows, and where there is
closure with valve leaflet/cusp coaptation. The result is valvular
insufficiency, as the valve tissue can no longer come together properly to
close the orifice. By providing a surgical shortening oftheannulus by placing
crimping sutures, or by sewing in a prosthetic ring (annuloplasty), the annulus
may be repaired with a decrease of insufficiency.
Aortic Valve
The 3 cusped valve separating the outflow tract ofthe left ventricle
from the aorta. The cusps attach to the annulus, and insert as thin fibrous
bands surfaced by endothelial cells (endocardium) into the aortic wall. These
fibrous bands, immediately adjacent to each other but separated by less than 1
mm, form 3 commissures. Dilatation of the root of the aorta, the area
immediately superior to the valve, may occur with connective tissue disease
(e.g. Marfan’s syndrome), atherosclerosis, or inflammation, and may lead to
aortic valvular insufficiency. In particular, with syphilis, Takayasu’s arteritis,
2
or rheumatoid arthritis, the inflammation and damage to these attachments
leads to commissural separation, thus preventing cusp coaptation. The area
behind the cusps, by the aortic surface, is a pocket known as the sinus of
Valsalva (see below).
The sinuses are potential sites of stasis, and with aging, they may
develop calcification followed by aortic valve degeneration with stenosis.
The sinuses also contain the two coronary ostia (see below). The aortic valve
is directly continuous with the ventricular surface ofthe mitral valve. Thus,
infection, or degeneration ofone valve can spread relatively easy to the other.
Apex, ventricle
A generally disregarded area of the heart, but one that may have
important functional significance. It is composed of the most dependent
portions ofboth left and right ventricles, with the myocardial fibers spiraling
towards the tip of the chamber. The muscle and the associated connective
tissue matrix (see below) come together as a button-like structure at this point.
In fact, during normal contraction there is dimpling ofthe apex (dimples in
the face are the result of connective tissue attachments between skeletal
muscle and the dermis). It appears that the apex serves as a fulcrum for
muscle shortening; thus, damage to the apex may have significant adverse
consequences for ventricular contractile function, by ‘untethering’ the distal
chamber attachments. Since the coronary supply to the apex is dependent on
vessels derived from all 3 coronary arteries, obstruction ofany one vessel may
lead to either generalized infarction or no damage, depending on the collateral
inter-connections between the vessels.
Atrio-ventricular node
A modified mass of myocardial cells that serves as the electrical
pacemaker ofthe ventricles. Situated in the lower inter-atrial septum, it lies
immediately superior to the tricuspid valve and its annulus and the mitral
valve and its annulus. Blood supply is provided by a branch of the right
coronary artery in most individuals, or a branch ofthe circumflex artery in the
minority of cases. Thus disease ofeither vessel may lead to ischemic damage
to the node, with the potential for conduction block. The node sends a bundle
of fibers into the ventricles (the bundle ofHis, see below), by penetrating the
annulus of the tricuspid and mitral valves. Thus, partial or complete heart
block may occur with disease processes involving the annulus such as calcific
degeneration ofthe annulus, infection, or surgical trauma following prosthetic
valve replacement orrepair ofa congenital defect.
3
