Download Pathology of the Heart

Pathology of the Heart
Contents - Structure:
1.
2.
3.
4.
5.
Congenital Heart Disease
Endocarditis/Nonbacterial vegetations
Valvular Heart Disease
Cardiomyopathies
Myocarditis
1. Congenital Heart Disease
Congenital Heart Disease
CHD is a general term used to describe abnormalities of the heart or great vessels that
are present from birth.
Most CHD arise from faulty embryogenesis during gestational weeks 3 through 8, when
major cardiovascular structures develop.
The most severe anomalies may be incompatible with intrauterine survival; however,
most others are associated with live births.
Some may produce menifestations soon after birth; others, however, do not necessarily
become evident until adulthood.
Most forms are now amenable to surgical repair with good results. The population of
adults with CHD is increasing rapidly. In this population CHDs represent an increased
risk of endocarditis, thrombotic lesions and arrhythmias.
Congenital Heart Disease


CHD is the most common type of heart disease
among children.
The incidence is 6 to 8 per 1000 full-term liveborn. The incidence is higher in premature
infants.
Congenital Heart Disease
CHD fall primarily into 3 major catagories:
1) Malformations causing a left-to-right shunt
2) Malformations causing a right-to-left shunt
3) Malformations causing an obstruction
A shunt is an abnormal communication between chambers or blood vessels.
Abnormal channels permit the flow of blood from right to left or the reverse,
depending on pressure relationships. When blood from the left side of the heart
enters the right side (left-to-right shunt), pulmonary blood flow increases, which
can result in pulmonary hypertension followed by right ventricular hypertrophy
and potentially failure. During the pulmonary hypertension, the muscular
pulmonary arteries first respond to increased pressure by medial hypertrophy
and vasoconstriction helping to prevent pulmonary edema. Prolonged
pulmonary arterial vasoconstriction stimulates the development of irreversible
obstructive intimal lesions. The defects accompanied by left-to-right shunt are
not initially associated with cyanosis (dusky blueness of the skin and mucous
membranes).
Congenital Heart Disease
Eventuaally, pulmonary vascular resistance and pressures increases toward systemic
levels, thereby reversing the shunt to right-to-left with unoxygenated blood develops
(late cyanotic CHD or Eisenmenger syndome). Once significant irreversible pulmonary
hypertension appears, the structural defects of CHD are considered irreparable.
In contrast, right-to-left shunt results in cyanosis, because there is diminished
pulmonary blood flow and poorly oxygenated blood enters the systemic circulation
(called cyanotic CHD). Moreover, with this shunt, bland or septic emboles arising in
peripheral veins can bypass the normal pulmonary flow and thus directly enter the
systemic circulation (paradoxical embolism). Clinical findings frequently associated with
severe, long-standing cyanosis include clubbing of the tips of the fingers and toes
(hypertrophic osteoarthropathy) and polycytemia.
Some developmental anomalies of the heart produce obstuctions to flow because of
abnormal narrowings of chambers, valves, or blood vessels. Examples are valvulare
stenoses (partial obstructions) or atresias (complete occlusions). These anomalies are
called obstructive congenital heart disease
Congenital Heart Disease
LEFT-TO-RIGHT SHUNTS - LATE CYANOSIS
A) Atrial Septal Defect (ASD)
ASD is an abnormal opening in the atrial septum that allows
communication of blood between the left and right atria. ASD is usually
asymptomatic until adulthood. The 3 major types are classified
according to their location in the septum: Secundum ASD – oval fossa
near the mid-septum, accounting for approximatelly 90% of all ASDs,
primum ASD – occurs adjacent to the AV valves (5% of ASDs), sinus
venosus ASD – located near the entrance of the superior vena cava.
Congenital Heart Disease
LEFT-TO-RIGHT SHUNTS - LATE CYANOSIS
B) Ventricular Septal Defect (VSD)
VSD allows free communication between right and left ventricles. VSD
is the most common congenital cardiac anomaly. About 70% of VSD
are associated with other structural defects such as tetralogy, about
30% occur as isolated anomalies. Depending on the size of the defect,
it may produce difficulties virtually from birth or, with smaller lesions,
may not be recognized until later or may even spontanely close. VSDs
are classified according to size and location. About 90% involve the
region of the membranous septum (membranous VSD). The remainder
lie below the pulmonary valve (infundibular VSD) or within the
muscular septum (muscular VSD). Although most often single, VSDs in
the muscular septum may be multiple (so-called Swiss-cheese
septum).
Congenital Heart Disease
LEFT-TO-RIGHT SHUNTS - LATE CYANOSIS
C) Patent Ductus Arteriosus (PDA)
PDA is a persistence after birth of the normal communication between
the pulmonary arterial system and the aorta of the fetus. About 90% of
PDAs occurs as an isolated anomaly. The remainder are most often
associated with VSD, coarctation, or pulmonary or aortic stenosis.
Congenital Heart Disease
LEFT-TO-RIGHT SHUNTS - LATE CYANOSIS
D) Atrioventricular Septal Defect (AVSD)
AVSDs result from abnormal development of the embryonic AV
canal, resulting in incomplete closure of the AV septum and
inadequate formation of the tricuspid and mitral valves. The most
common forms are partial AVSD – consisting of a primum ASD and
cleft anterior mitral leaflet causing mitral insufficiency, and complete
AVSD – consisting of a large combined AVSD and a large common
AV valve
Congenital Heart Disease
RIGHT-TO-LEFT SHUNTS - EARLY CYANOSIS
A) Tetralogy of Fallot
The 4 features of the Fallot tetralogy are:
1. Ventricular septal defect,
2. Obstruction to the right ventricular outflow tract (subpulmonary
stenosis),
3. An aorta that overrides the VSD, and
4. Right ventricular hypertrophy.
Digital clubbing with cyanotic
nail beds in an adult with
tetralogy of Fallot
RIGHT-TO-LEFT SHUNTS - EARLY CYANOSIS
B) Transposition of Great Arteries
TGA implies ventriculoarterial discordance, such that the aorta
arises from the right ventricle, and the pulmonary artery
emanates from the left ventricle.
Without surgery, most patients die within the first months of life.
Currently, most patients undergo a reparative operation during the
first several weeks of life.
Congenital Heart Disease
RIGHT-TO-LEFT SHUNTS - EARLY CYANOSIS
C) Persistent Truncus Arteriosus
PTA arises from a developmental failure of separation of the
embryonic truncus arteriosus into aorta and pulmonary artery.
Congenital Heart Disease
RIGHT-TO-LEFT SHUNTS - EARLY CYANOSIS
D) Tricuspid Atresia
TA is complete occlusion of the tricuspid valve orifice. The lesion is
almost always associated with underdevelopment (hypoplasia) of the
right ventricle. Cyanosis is present virtually from birth, and there is a
high mortality in the first weeks or months of life.
Congenital Heart Disease
RIGHT-TO-LEFT SHUNTS - EARLY CYANOSIS
E) Total Anomalous Pulmonary Venous Connection
No pulmonary veins directly join the left atrium, only primitive
systemic venous channels from the lungs to the left innominate vein
or to the coronary sinus. Either a patent foramen ovale or an
atrioventricular septal defect is always present, allowing pulmonary
venous blood to enter the left atrium. Consequences of TAPVC
include volume and pressure hypertrophy and dilatation of the right
atrium and right ventricle. The left atrium is hypoplastic, but the left
ventricle is usually normal in size. Cyanosis may be present, owing
to mixing of well-oxygenated and poorly oxygenated blood.
Congenital Heart Disease
OBSTRUCTIVE CONGENITAL ANOMALIES
A) Coarctation of Aorta
CA (narrowing, constriction of the aorta) ranks high in frequency among the
common structural anomalies.
Males affected twice as often as females.
Two classic forms have been described:
1. An infantile – with tubular hypoplasia of the aortic arch proximal to a patent
ductus arteriosus (it is often symptomatic in early childhood),
2. An adult – with a discrete ridgelike infolding of the aorta.
Clinical manifestation depend almost on the severity of the narrowing and the
patency of the ductus arteriosus. Most of the children are asymptomatic, and the
disease may go unrecognized into adult life. Typically, there is hypertension in the
upper extremities, but there are weak pulses and lower blood pressure in the lower
extremities, associated with manifestations of arterial insufficiency (i.e.,
claudication and coldness). Particularly characteristic in adults is the development
of collateral circulation between the precoarctation arterial branches and the
postcoarctation arteries and the radiographically visible erosions of the ribs.
Congenital Heart Disease
OBSTRUCTIVE CONGENITAL ANOMALIES
B) Pulmonary Stenosis and Atresia
PSA is a relatively frequent malformation. PSA constitutes an
obstruction at the pulmonary valve, which may be mild to severe. It
may occur as an isolated defetc or as part of a more complex
anomaly – tetralogy of Fallot or transposition of great arteries. Right
ventricular hypertrophy often develops. Mild stenosis may be
asymptomatic and compatible with long life, the most severe
stenosis is the cyanotic.
Congenital Heart Disease
OBSTRUCTIVE CONGENITAL ANOMALIES
C) Aortic Stenosis and Atresia
ASA constitutes the narrowings and obstructions of the aortic valve present
from birth. There are 3 major types of stenosis:
1. Valvular – the cusps may be hypoplastic, dysplastic or abnormal in
number, less severe degrees of this stenosis may be compatible with
long life. In severe forms, obstruction of the left ventricular outflow tract
leads to hypoplasia of the left ventricle and ascending aorta =
hypoplastic left heart syndrome (is nearly always fatal in the first week
of life).
2. Subvalular – represents either a thickened ring (discrete type) or collar
(tunnel type) of dense endocardial fibrous tissue below the level of the
cusps.
3. Supravalvular – represents an inherited form of aortic dysplasia in which
the ascending aortic wall is greatly thickened, causing luminal
constriction. Recent studies suggest that mutation in the elastin gene
can cause supravalvular aortic stenosis.
A prominent systolic murmur is usually detectable.
Pressure hypertrophy of the left ventricle develops as a consequence of the obstruction to
blood flow.
2. Endocarditis/Nonbacterial
vegetations
Infective Endocarditis
• 100% fatal if undiagnosed and untreated
• 20% fatal if diagnosed and treated
• uncommon
• primarily in adults
• commonly with underlying heart disease

Gross pathology of subacute bacterial endocarditis involving mitral valve. Left
ventricle of heart has been opened to show mitral valve fibrin vegetations due
to infection with Haemophilus parainfluenzae. Autopsy.
Infective Endocarditis
• 70% streptococcal
• 20% staphylococcal
• Mitral > Aortic > Right
• The bigger the vegetation,
the more likely it is infected.
Infective Endocarditis
Symptoms
Fever
Chills
Weakness
Dyspnea
(80%)
(40%)
(40%)
(40%)
Infective Endocarditis
Signs
Fever
(90%)
Heart Murmur
(85%)
Splenomegaly
(30%)
Petechiae
(30%)
Infective Endocarditis
Uncommon (1/1000 hospital admissions)
Primarily a disease of adults (median age 50)
Male predominance (male : female ratio 1.7 : 1)
100% fatal if undiagnosed and untreated
20% fatal if diagnosed and treated
appropriately (IV antibiotics =/- surgery)
Infective Endocarditis
Most commonly of the valves,
with “vegetations” = friable masses of
infecting organisms and blood clot
Pathogenesis:
1. Valvular endothelial injury
2. Platelet + fibrin deposition
3. Microbial seeding
4. Microbial multiplication
Up to 1010 bugs/gm (mature)
Infective Endocarditis: 3 classifications
1.
Acute Bacterial Endocarditis (“ABE”)
usually fulminant, due to highly virulent
organisms (e.g. Staphylococcus aureus)
versus
Subacute Bacterial Endocarditis (“SBE”)
with insidious onset over weeks, due to less
virulent organisms (e.g. viridans streptococci)
Infective Endocarditis: 3 classifications
2.
Native Valve Endocarditis (“NVE”)
versus
Prosthetic Valve Endocarditis (“PVE”)
[commonly due to coagulase-negative
Staphylococcus epidermidis, rare in NVE]
versus
Endocarditis in Intravenous Drug Users
[commonly acute and commonly tricuspid]
Infective Endocarditis: 3 classifications
3. According to the specific infecting organism:
(e.g. Pseudomonas aeruginosa endocarditis)
Infective Endocarditis
70% have predisposing heart disease
Mitral valve prolapse
Congenital disease
Prosthetic valve
Degenerative disease
Rheumatic disease
Previous endocarditis
Infective Endocarditis
Left-sided valves
Right-sided valves
Both
Other
75%
15%
5%
5%
Infective Endocarditis
Mitral valve alone
Aortic valve alone
Mitral plus aortic
Tricuspid
Pulmonic
35%
20%
20%
14%
1%
Infective Endocarditis
Portals of Entry
Gingivitis, Chewing, Brushing teeth,
Central venous catheterization, Surgery,
Bladder catheterization, Endoscopy, Shaving,
Intravenous drug abuse, Ellis Island, etc.
Infective Endocarditis: Etiologic Agents
I.
Streptococci in general
70%
A. viridans group streptococci
(oral flora)
35%
B. Streptococcus bovis
15%
(associated with colon cancer)
C. Enterococci
10%
(enteric flora)
D. Other streptococci
10%
Infective Endocarditis: Etiologic Agents
II. Staphylococci in general
A. S. aureus = coagulase-positive
20%
18%
III. HACEK group bacteria
4%
(fastidious slow-growing oral flora)
IV. Other gram-negative aerobes
3%
V. Fungi (Candida = most common)
2%
Infective Endocarditis
Gross Pathology
Large (up to 3 cm), friable,
tan grey red or brown vegetations,
single or multiple,
usually on line of valve closure
(atrial side atrioventricular valves,
ventricular side semilunar valves)
Infective Endocarditis
Gross Pathology
+ / - perforation of valve
+ / - adjacent abscess
+ / - fibrotic scarring
+ / - calcification
Infective Endocarditis
Microscopic Pathology
Fibrin, platelets, masses of organisms,
+/- necrosis, +/- neutrophils
Later: +/-lymphocytes, +/- macrophages,
+/- fibroblasts, +/- fibrosis
Infective Endocarditis
Continuous low-grade bacteremia is
characteristic of endocarditis.
You don’t need a lot of blood
cultures to make the diagnosis, but
you should alert the microbiology
laboratory that endocarditis is suspected.
Endocardial Disease
D. INFECTIVE ENDOCARDITIS
IE is one of the most serious of all infections. IE is characterized by colonization
or invasion of the heart valves, the mural endocardium, or other cardio-vascular
sites by a microbiologic agents (bacteria, fungi, rickettsiae), leading to the
formation of bulky, friable vegetation composed of thrombotic debris and
microbes, often associated with destruction of the underlying cardiac tissues.
The endocarditis has been classified on clinical grounds into acute and
subacute forms, reflecting the range of disease severity, its tempo and the
virulence of the infecting microorganisms. Clinical Features: Fever, murmurs,
petechiae etc. Morphology: Vegetations, destruction of valves, systemic emboli,
sepsis, septic infarcts. Complications: Cardiac (valvular insufficiency or
stenosis, cardiac failure, myocardial ring abscess with possible perforation of
aorta, suppurative pericarditis), embolic (to the brain, heart, spleen, kidneys
etc.), renal (embolic infarction, focal and diffuse glomerulonephritis, multiple
abscesses).
A: Gross photograph of a mitral valve specimen from a patient with
Staphylococcus aureus endocarditis; note the vegetations and
distortion of the valve. B: A photomicrograph shows the process
involving the leaflet and chordae.
Pathology of the heart
Endocardial Disease
E. NONINFECTED VEGETATIONS
C.1. Nonbacterial Thrombotic Endocarditis
NBTE is characterized by the deposition of small masses of fibrin, platelets,
and other blood components on the leaflets of the cardiac valves. In
contrast to the vegetations of infective endocarditis, the valvular lesions of
NBTE are sterile. NBTE is often encountered in patients with cancer or
sepsis – marantic endocarditis. The local effect on the valves is
unimportant, clinical significance results from emboli and infarcts of brain,
heart etc. producting. In pathogenesis, a hypercoagulable state with
systemic activation of blood coagulation such as disseminated intravascular
coagulation (DIC) may be involved.
C.2. Endocarditis of Systemic Lupus Erythematosus (Libman-Sachs
Endocarditis)
Mitral and tricuspid valvulitis with small, sterile vegetations.

The small pink vegetation on the rightmost cusp margin
represents the typical finding with non-bacterial thrombotic
endocarditis (or so-called "marantic endocarditis"). This is noninfective. It tends to occur in persons with a hypercoagulable
state (Trousseau's syndrome, a paraneoplastic syndrome
associated with malignancies) and in very ill persons.

The valve is seen on the left,
and a bland vegetation is seen
on the right. It appears pink
because it is composed of fibrin
and platelets. It displays about
as much morphologic variation
as a brown paper bag. Such
bland vegetations are typical of
the non-infective forms of
endocarditis.

Here is another marantic
vegetation on the leftmost cusp.
These vegetations are rarely
over 0.5 cm in size. However,
they are very prone to embolize.

Libman-Sacks endocarditis (and mitral rheumatic valvulitis)
Here are flat, pale tan, spreading vegetations over the mitral valve surface
and even on the chordae tendineae. This patient has systemic lupus
erythematosus. Thus, these vegetations that can be on any valve or even on
endocardial surfaces are consistent with Libman-Sacks endocarditis.
These vegetations appear in about 4% of SLE patients and rarely cause
problems because they are not large and rarely embolize. Note also the
thickened, shortened, and fused chordae tendineae that represent remote
rheumatic heart disease.
Endocardial Disease
F. CARCINOID HEART DISEASE
Principally involving the endocardium and valves of the right side of the
heart. Cardiac lesions (fibrous intimal thickenings on the inside surfaces
of the cardiac chambers and valvular leaflets) involve one half of
patients with the carcinoid syndrome.
3. Valvular Heart Disease
Pathology of the heart
Endocardial Disease
Valvular involvement by disease causes stenosis, insufficiency
(regurgitation), or both. Vascular insufficiency may result from either
intrinsic disease of valve cusps or damage to or distortion of the
supporting structures (aorta, mitral annulus, papillary muscles...). It
may appear acutely with infective endocarditis or chronically with
scarring and retraction. In contrast, valvular stenosis almost always is
due to a primary cuspal abnormality and is virtually always a chronic
process.
Pathology of the heart
Endocardial Disease
The most frequent chronic causes of the major functional valvular
lesions are as follows:
mitral stenosis – rheumatic heart disease,
mitral insufficiency – myxomatous degeneration,
aortic stenosis - calcification of aortic valves,
aortic insufficiency – dilatation of the ascending aorta.
Pathology of the heart
Endocardial Disease
A. VALVULAR DEGENERATION CAUSED BY CALCIFICATION
Calcific aortic stenosis (acquired, senile), calcification of a congenitally
bicuspid aortic valve, mitral annular calification.
B. MYXOMATOUS DEGENERATION OF THE MITRAL VALVE (M. V.
PROLAPSE)
Complication - infective endocarditis, mitral insufficiency requiring
surgery, stroke or other systemic infarct resulting from embolism of
leaflet or atrial wall thrombi, and/or arrhythmias.
C. RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE
RF is an acute, immunologically mediated (hypersensitivity reaction), multisystem
inflammatory disease that occurs a few weeks after an episode of group A
(beta-hemolytic) streptococcal infection and often involves the heart.
Acute rheumatic carditis, which complicates the active phase of rheumatic fever,
may progress to chronic valvular deformities.
RF is characterized by a constellation of findings that includes as major
manifestations
(1) migratory polyarthritis of the large joints,
(2) carditis,
(3) subcutaneous nodules,
(4) erythema marginatum of the skin, and
(5) Sydenham chorea - a neurologic disorder with involuntary purposeless, rapid
movements.
The most important consequence of RF is chronic rheumatic
heart disease, characterized by deforming fibrotic valvular
disease (particularly mitral stenosis), which can produce
permanent dysfunction and severe, sometimes fatal, cardiac
dysfunctions decades later.
Morphology: Aschoff bodies (nodules) – foci of fibrinoid
degeneration surrounded by lymphocytes and histiocytes
(multinucleated form of histiocytes is called Aschoff giant
cells). Concomitant involvement of the endocardium and the
left-sided valves (fibrinoid necrosis with formation of verrucalike vegetations) may cause a rare emboli and valve
deformations. Subendocardial lesions may induce irregular
thickenings in the left atrium called MacCallum plagues.
Nikolai Nikolajewitsch
Anitschkow
Russian pathologist, born
November 3, 1885; died
December 7, 1964

The small verrucous vegetations seen along the
closure line of this mitral valve are associated with
acute rheumatic fever. These warty vegetations
average only a few millimeters and form along the
line of valve closure over areas of endocardial
inflammation. Such verrucae are too small to cause
serious cardiac problems.

The heart has been sectioned to reveal the mitral
valve as seen from above in the left atrium. The
mitral valve demonstrates the typical "fish mouth"
shape with chronic rheumatic scarring. Mitral valve is
most often affected with rheumatic heart disease,
followed by mitral and aortic together, then aortic
alone, then mitral, aortic, and tricuspid together.
4. Cardiomyopathies
Cardiomyopathies
“A primary disorder of the heart muscle
that causes abnormal myocardial
performance and is not the result of
disease or dysfunction of other cardiac
structures … myocardial infarction,
systemic hypertension, valvular stenosis
or regurgitation”
Classification

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
etiology
gross anatomy
histology
genetics
biochemistry

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immunology
hemodynamics
functional
prognosis
treatment
WHO Classification

Unknown cause
(primary)




Dilated
Hypertrophic
Restrictive
unclassified

Specific heart
muscle disease
(secondary)

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



Infective
Metabolic
Systemic disease
Heredofamilial
Sensitivity
Toxic
Br Heart J 1980; 44:672-673
Functional Classification

Dilatated (congestive, DCM, IDC)


Hypertrophic (IHSS, HCM, HOCM)


ventricular enlargement and syst
dysfunction
inappropriate myocardial hypertrophy
in the absence of HTN or aortic stenosis
Restrictive (infiltrative)

abnormal filling and diastolic function
Graphic representation of the three distinctive and
predominant clinical-pathologic-functional forms of
myocardial disease.
Idiopathic Dilated
Cardiomyopathy



a disease of unknown etiology that
principally affects the myocardium
LV dilatation and systolic dysfunction
pathology



increased heart size and weight
ventricular dilatation, normal wall thickness
heart dysfunction out of portion to fibrosis
Incidence and Prognosis



3-10 cases per 100,000
20,000 new cases per year in the U.S.A.
death from progressive pump failure
1-year
2-year
5-year


25%
35-40%
40-80%
stabilization observed in 20-50% of
patient
complete recovery is rare
Clinical Manifestations

Highest incidence in middle age




blacks 2x more frequent than whites
men 3x more frequent than women
symptoms may be gradual in onset
acute presentation


misdiagnosed as viral URI in young adults
uncommon to find specific myocardial
disease on endomyocardial biopsy
Dilated cardiomyopathy. A, Gross photograph. Four-chamber dilatation and
hypertrophy are evident. There is granular mural thrombus at the apex of the left
ventricle (on the right in this apical four-chamber view). The coronary arteries were
unobstructed. B, Histology demonstrating variable myocyte hypertrophy and
interstitial fibrosis (collagen is highlighted as blue in this Masson trichrome stain).
Biopsy findings consistent with idiopathic dilated cardiomyopathy. A:
Marked myocyte hypertrophy. B: Irregular hypertrophy. C: Focal,
particularly subendocardial replacement and interstitial fibrosis.
Severe Adriamycin effect is seen in this 1-mm thick section (A)
stained with toluidine blue. The electron micrograph (B) shows
sarcotubular dilation, one of the earlier changes.
Hypertrophic Cardiomyopathy




First described by the French and Germans
around 1900
uncommon with occurrence of 0.02 to 0.2%
a hypertrophied and non-dilated left ventricle
in the absence of another disease
small LV cavity, asymmetrical septal
hypertrophy (ASH), systolic anterior
motion of the mitral valve leaflet (SAM)
65%
35%
10%
www.kanter.com/hcm
Familial HCM



First reported by Seidman et al in 1989
occurs as autosomal dominant in 50%
5 different genes on at least 4
chromosome with over 3 dozen
mutations




chromosome
chromosome
chromosome
chromosome
14 (myosin)
1 (troponin T)
15 (tropomyosin)
11 (?)
Pathophysiology
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Systole
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Diastole

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dynamic outflow tract gradient
impaired diastolic filling,  filling pressure
Myocardial ischemia
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 muscle mass, filling pressure, O2 demand
 vasodilator reserve, capillary density
abnormal intramural coronary arteries
systolic compression of arteries
Hypertrophic cardiomyopathy. High-power photomicrograph of
marked myocyte hypertrophy and disarray from a septal region
Restrictive Cardiomyopathy

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Hallmark: abnormal diastolic function
rigid ventricular wall with impaired
ventricular filling
bear some functional resemblance to
constrictive pericarditis
importance lies in its differentiation
from operable constrictive pericarditis
Classification


Idiopathic
Myocardial
1. Noninfiltrative
 Idiopathic
 Scleroderma
2. Infiltrative
 Amyloid
 Sarcoid
 Gaucher disease
 Hurler disease

3. Storage Disease
 Hemochromatosis
 Fabry disease
 Glycogen storage
Endomyocardial
 endomyocardial
fibrosis
 Hyperesinophilic synd
 Carcinoid
 metastatic
malignancies
 radiation,
anthracycline
Restriction vs Constriction
History provide can important clues
 Constrictive pericarditis
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Restrictive cardiomyopathy

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history of TB, trauma, pericarditis, sollagen
vascular disorders
amyloidosis, hemochromatosis
Mixed

mediastinal radiation, cardiac surgery
Secondary KMP (specific
diseases of myocardium)
-
Despite different etiology morphology of dilated cardiomyopathy
Metabolic disorders
- hemochromatosis, calcinosis,
amyloidosis, glykogenosis
Endocrine disorders
- hyperthyreosis, hypothyreosis,
acromegaly, pheochromocytoma
- Duchenn muscular dystrophy
- some drugs (cytostatics adriamycin,
cyclophosphamide)
- accumulation of small lipid droplets of
neutral fat in the cytoplasm,
Muscle dystrophies
Intoxication
Steatosis
Amyloidosis involving the myocardium. The marked atrophy of the
myocytes caused by the interstitial infiltrate can be appreciated in
longitudinal (A) and transverse (B) sections of the myocardium. C:
Ultrastructural studies confirm the nature of the interstitial infiltrate. D:
Involvement may be quite focal and microscopic.
Cardiac storage diseases
with
intracellular depositions. A: Extensive
iron deposits are seen (Pearl iron
stain). B: Vacuolated myocytes in an
endomyocardial biopsy specimen
obtained from a female patient
heterozygous for Fabry disease. C:
Typical
lamellar
intracellular
inclusions are seen ultrastructurally.
ADRV

Arrythmogenic right ventricular cardiomyopathy. A, Gross photograph,
showing dilation of the right ventricle and near transmural replacement
of the right ventricular free-wall myocardium by fat and fibrosis. The
left ventricle has a virtually normal configuration. B, Histologic section
of the right ventricular free wall, demonstrating replacement of
myocardium (red) by fibrosis (blue, arrow) and fat (collagen is blue in
this Masson trichrome stain).
5. Myocarditis
Myocarditis
Inflammatory disease of myocardium with necrosis
and/or degeneration of muscle cells (Dallas criteria)




Isolated
Connected to inflammation elsewhere in body
Quite rare, mainly affecting children and young
adults
Morphology



cellular infiltrate
Necrosis of adjacent muscle fibers
Mostly healing without consequences, sometimes
progression , heart failure, death.
Myocarditis and
cardiomyopathies
infectious
 viral
 Most often - Coxsackie B, A, ECHO, influensa, CMV,
HIV,..
 Upper respiratory tract infection precedes
 Diagnostics





serology … titer Ab
Molecular biology PCR of viral DNA/RNA
Isolation of viral agent
BUT : in the time of diagnosis the agent not present in tissue
Pathogenesis

Direct destruction of cells by virus ( cytopathic effect), indirectly by T-cell
immune reaction (in Coxsackie this type of destruction more often) in
lateg stage autoimmune reaction
Myocarditis



Most often changes hypereosinophilia,
serous exudate, scattered inflammatory
cells.
Later destruction of muscle cells, T
cells, histiocytes
Final stage intersticial fibrosis with
compensatory hypertrophy of heart
This series of photomicrographs illustrates different forms of myocarditis.
A: Severe diffuse myocarditis. B: Diffuse myocarditis with fibrosis. C: Focal
myocarditis. D: Diffuse myocarditis with a prominent eosinophilic infiltrate.
Myocarditis. A, Lymphocytic myocarditis, with mononuclear inflammatory cell infiltrate and associated
myocyte injury. B, Hypersensitivity myocarditis, characterized by interstitial inflammatory infiltrate
composed largely of eosinophils and mononuclear inflammatory cells, predominantly localized to
perivascular and large interstitial spaces. This form of myocarditis is associated with drug hypersensitivity.
C, Giant cell myocarditis, with mononuclear inflammatory infiltrate containing lymphocytes and
macrophages, extensive loss of muscle, and multinucleated giant cells. D, The myocarditis of Chagas
disease. A myofiber is distended with trypanosomes (arrow). There is a surrounding inflammatory reaction
and individual myofiber necrosis.
Myocarditis




bacterial
Following septicopyemy
- most often staphylococci – endocarditis, embol.abscesses in myocardium
- exotoxin Corynebacterium diphteriae
- in Lyme disease -Borrelia burgdorferi –
Infektotoxic (diphteria type)

exotoxin interferes with carnitin transport of fatty acids and destruction of
proteosynthesis on ribosomes

Patchy necrosis of cardiomypcytes, eosinophilia, steatosis

Serous inflammation, lymphoplasmocellular inflammation

Mainly right ventricle affected
Infektoallergic

3 weeks after infection, type IV hypersensitivity, right ventricle

Mycotic


mainly Candida – immunocompromised patients
Parasitic



toxoplasmosis - Toxoplasma gondii (AIDS)
Chagas disases - Trypanosoma cruzi (South
America)
Early patchy necrosis of myocardium,
lymphocytes, macrophages, pseudocystes in
muscle fibres, left ventricle dilation.
Myocarditis caused by intracellular
parasites. A: Multifocal myocarditis
caused by Trypanosoma cruzi (Chagas
disease) is seen on low power. B: High
power
shows
the
intracellular
organisms inside a myocyte, which is
often not associated with an adjacent
inflammatory reaction. C: Toxoplasma
gondii infection in a patient with
acquired immunodeficiency syndrome.
A: A fibrinous interstitial infiltrate is seen in
Pneumocystis carinii infection. B: Silver stain
demonstrates the offending organisms (Grocott
methenamine silver stain).
Non-infectious
Drug hypersensitivity
•
Antibiotics, antiflogistics, antiepileptics
•
Eosinophil myocarditis
Granulomatous
Granulomas of sarcoid type, left ventricle and septum involved
Acute idiopatic giant cell myocarditis Fiedler
Young men around 20 years of age
lymphocytic-histiocytic inflammation, multinuclear giant cells or heart
muscle origin
Sarcoidosis involving the myocardium.