Pathology of Rheumatic heart disease,

infective endocarditis and valvular heart

disease

Sufia Husain
Department of Pathology
KSU, Riyadh
February 2018
References: Robbins Basic Pathology and Rubin’s Pathology
Objectives:
At the end of this lecture, the students should be able to:
(1)Understands the clinicopathological features of rheumatic heart disease which is a
major cause of acquired mitral and aortic valve diseases in the Kingdom of Saudi
Arabia.
(2)Know the pathological causes and pathophysiological consequences of stenosis
and incompetence of all the cardiac valves but particularly the mitral and aortic
valves.
(3) Understands the pathology of infective endocarditis so as to be able to identify
patients at risk and when appropriate ensure prophylactic treatment is given.

Key principles to be discussed:

(1) Pathology and manifestations of rheumatic heart disease as a major cause of

valvular diseases in the Middle East and Saudi Arabia.
(2) Complications of rheumatic heart disease including atrial fibrillation, valvular
and atrial thrombus formation with systemic embolism, cardiac failure and infective
endocarditis.
(3) Infective endocarditis: predisposing factors, clinical acute and subacute
forms, common pathogenic bacteria in IE and complications including valve
perforation, thrombosis and septic embolization of the vegetations.
(4) Causes and consequences of valvular heart disease with special emphasis on
aortic and mitral valve including "floppy or prolapsed" mitral valve.
RHEUMATIC HEART DISEASE

Rheumatic heart disease is a heart disease caused by

rheumatic fever.
Rheumatic heart disease can be
acute or
chronic
ACUTE Rheumatic Fever
 ACUTE Rheumatic Fever
 Definition: Rheumatic fever (RF) is
an acute, immune mediated, multi-system inflammatory disease that occurs a
few weeks after, group A-beta hemolytic streptococcal infection.
It is an acute post-streptococcal non-suppurative inflammatory disease with
cardiac and extracardiac manifestations.
The inflammation is mainly in the heart, joints, central nervous system and
skin.
Occurs in only 3% of patients with group A streptococcal pharyngitis.
It is seen mainly in children, 5 to 15 years of age.
Rheumatic fever is a major health problem in 3rd world countries and in
crowded, low socioeconomic urban areas.
The incidence and mortality of rheumatic fever has declined over the past 30
years (due to improved socioeconomic condition and rapid diagnosis and
treatment of strep. pharyngitis).
Etiopathogenesis:
The pathogenesis of RF remains unclear and is not yet
completely understood.
It is linked to streptococcal infection. Disease occurs 1 to 5
weeks after pharyngeal infection by Group A beta -Hemolytic
Streptococcus.
It is most likely an immune mediated process in which  the
causative organisms (streptococci) stimulates in the formation
of antibodies  these antibodies cross react with certain
antigens present in the heart and joints (because these
antigens are similar to streptococcal antigen)  the antigen
antibody reaction leads to inflammation.
Repeated attacks or a single severe attack can lead to 
chronic rheumatic heart disease leading to  cardiac failure.
Strep throat
Antibody
production

Antibody cross-reaction
with heart

vegetations Aschoff body pericarditis

Cardiac manifestations of rheumatic FEVER
(also called as acute rheumatic heart disease or acute rheumatic carditis/ pancarditis)
There is a pancarditis in which there is inflammation in all three layers of the heart
(endocardium, myocardium and pericardium)
1. Pericarditis: inflammation of pericardium  fibrinous or serofibrinous secretion
in the pericardium. These secretion collect between the visceral and parietal
pericardium like butter between two slices bread and therefore also called "bread
and butter” pericarditis.
2. Myocarditis: inflammation of myocardium  many Aschoff bodies. Can cause
sudden death.
3. Endocarditis: inflammation of the endocardium including the heart valves
(valvulitis) and chordae tendineae  results in fibrin deposition on valve leaflets
forming tiny thrombi along lines of closure called rheumatic vegetations. Mitral
and aortic valve are mainly involved. Aschoff bodies/nodules are uncommon
in the valves. This acute inflammation may either resolve completely or progress
to scarring with development of chronic fibrotic deformities of the heart valves and
chordae tendineae leading to chronic rheumatic heart disease many years later.
4. Subendocardial lesions can also be seen, commonly in the left atrium called as
MacCallum plaques.
 Aschoff bodies
 The characteristic lesion of acute rheumatic
fever are the Aschoff bodies.
 Aschoff bodies are multiple tiny
granulomatous lesions of the heart. They are
situated next to small arteries and are
characteristically seen in the myocardium
(rheumatic myocarditis).
 An Aschoff body, consists of:
a focus of eosinophilic collagen necrosis
(representing the site of antibody-antigen
reaction),
plump activated macrophages/ histiocytes
called Anitschkow/ caterpillar cells. Some
of the macrophages become multinucleated
to form Aschoff giant cells.
chronic inflammation.
 Aschoff bodies are found mainly in the
myocardium and pericardium. Uncommon in the
endocardium and heart valves.
 They ultimately "heal" by fibrosis resulting in a
nodule of scar tissue.
Rheumatic Vegetations:

1. Tiny (size of a pin’s head), sessile arranged in a row and firmly fixed with the underlying tissue.
2. These are situated in the valve cusp, a few millimeters away from the free margin (this is the most traumatized area).

tatic.wikidoc.org/1/1e/Rheumatic_fever_003.jpg
Extra cardiac manifestations of Rheumatic Fever:
Involvement of Other Organs
 Joints:
 Arthralgia
 Migratory polyarthritis which is "fleeting arthritis" in the
large joints e.g. knee, ankle, elbow wrist etc. It is self
limiting with no chronic deformities. Aschoff bodies may
be present in the synovial membrane, joint capsule,
ligament etc. with joint effusion.
 Skin: skin nodules, erythema marginatum.
 Subcutaneous tissue: Rheumatic nodules mainly seen
over the bony prominences e.g. knuckle, elbow, patella etc.
 Neurologiocal disorder: Sydenhem’s chorea (St. Vitus'
dance) characteristized by series of rapid involuntary
purposeless movements of the face and arms. This occurs
late in the disease.
 Lung: uncommon, chronic interstitial inflammation and
fibrinous pleuritis.
 Acute Rheumatic Fever: Clinical features

 Peak incidence: 5-15 years.

 History of sore throat: symptoms start 10 days to 6 weeks after by
group A Streptococcal pharyngitis
 By that time the symptoms start the throat/ pharangeal cultures
are usually negative.
 Serum antistreptolysin O (ASO titer/ antibodies to group A
streptococcal antigens), anti-DNAase B, and antihyaluronidase
are raised and provide evidence of a recent infection with group
A Streptococcus.
 Acute symptoms usually subside within 3 months
 The mortality from acute rheumatic carditis is low.
There is no specific test for rheumatic fever. The diagnosis is made
based on the clinical findings when either:
1. two major or
2. one major and two minor
clinical features / criteria are met. This is called as the Jones
criteria.
Acute Rheumatic Fever: Clinical Features
continued….
JONES CRITERIA:
Major criteria/ clinical features
 Carditis (murmurs, pericardial friction rubs, weak heart sounds, tachycardia and
arrhythmias cardiomegaly, pericarditis, and congestive heart failure)
 Migratory polyarthritis of the large joints
 Erythema marginatum of the skin
 Subcutaneous nodules
 Sydenhem’s chorea (St. Vitus' dance)
Minor criteria / clinical features
 Previous rheumatic fever
 Arthralgia
 Fever
 Lab tests indicative of inflammation — ESR (erythrocyte sedimentation rate), CRP
(C-Reactive protein), leukocytosis
 EKG changes
CHRONIC RHEUMATIC HEART
DISEASE
 CHRONIC RHEUMATIC HEART
DISEASE
o The myocarditis and pericarditis components of RF typically
resolve without permanent sequelae.
o In contrast, the acute valvulitis or chordae tendinitis of rheumatic
fever heals by fibrosis (scarring) and result in irreversible deformity
of the involved cardiac valve and chordae tendineae. Severe
valvular scarring develops months or years after acute RF.
o Most harmful effect of rheumatic disease is due to involvement of
cardiac valves. The valve leaflets develop diffuse fibrosis, become
thickened, shrunken, and less movable which can lead to cardiac
failure, thromboembolism and infective endocarditis.
CHRONIC RHEUMATIC HEART DISEASE
Valves affected in chronic rheumatic heart disease:
 Left side of heart is more commonly involved than the right.
 mitral valve alone is most commonly affected
 followed by combined mitral/aortic valve
 Tricuspid valve is rarely affected.
 Pulmonary valve is practically never affected.
Type of damage
 fibrosis of valve leaflets  stenosis (Reduction of diameter)
 fibrosis of chordae tendineae  regurgitation (improper closure)
 Therefore patient can have mitral stenosis (most common), mitral
regurgitation, aortic stenosis and aortic regurgitation
Chronic Rheumatic heart disease:
Clinical features

Manifests years or decades after the initial episode

of rheumatic fever.
Signs and symptoms depend on the valve(s)
involved: cardiac murmurs, hypertrophy, dilation,
congestive heart failure, arrhythmia,
thromboembolism and infective endocarditis.
Treatment may require valve surgery.
Complications of Chronic Rheumatic
Valvular Heart Disease

 Bacterial infective endocarditis: the scarred valves of rheumatic

heart disease provide an attractive environment for bacteria to grow.
 Mural thrombi form in cardiac chambers. They give rise to
thromboemboli, which can produce infarcts in various organs.
 Congestive heart failure
 Adhesive pericarditis
 Atrial fibrillation.
siachnotes.wikidot.com
Infective Endocarditis
Infective Endocarditis (IE)
 Definition: infection of the cardiac valves or mural/ inner surface of the endocardium,
resulting in the formation of an adherent mass of thrombotic debris mixed with micro-
organisms.
 Infective endocarditis is a particularly difficult infection to eradicate because of the
avascular nature of the heart valves.
 IE is Divided into:
 Acute IE:
 Is caused by highly virulent organisms (staphylococcus aureus)
 infects even normal/healthy valves,
 progresses rapidly,
 Has little local host reaction.
 Subacute IE:
 It is an infection in a previously abnormal/ damaged valves by organisms of
low virulence (-hemolytic streptococci viridans),
 progresses slowly,
 It induces a local inflammatory reaction.
o Prognosis: depends to some extent on the offending organism and the stage at
which the infection is treated. About 1/3rd of cases of Staph. aureus endocarditis
are still fatal.
http://m.patient.media/images/127.gif
Risk factors of Infective Endocarditis:
1. In children: an underlying cardiac lesion (congenital heart disease is most
common).
2. In adults: More than half of adults with bacterial endocarditis have no predisposing
cardiac lesion. Mitral valve prolapse and congenital heart disease are the most
frequent cause for bacterial endocarditis in adults.
3. Rheumatic heart disease.
4. Intravenous drug abusers can end up injecting micro-organisms intravenously
when taking intravenous drugs, leading to IE. The tricuspid valve is infected in half
of cases. About 50% of the IE in IV drug abusers are caused by S. aureus.
5. People with prosthetic valves are at high risk of developing IE . Prosthetic valve
endocarditis is caused commonly by coagulase-negative staphylococci (e.g. S.
epidermidis).
6. Transient bacteremia from any procedure may lead to infective endocarditis e.g.
dental procedures, urinary catheterization, infected indwelling vascular catheters
gastrointestinal endoscopy, and obstetric procedures.
7. The elderly (due to degeneration of heart valves e.g. calcific aortic stenosis),
diabetics and pregnant women are at increased risk.
Infective Endocarditis:

Mitral valves are the most

common sites of IE
followed by aortic valve.
In IV drug users, the right
side valves (tricuspids) are
more commonly involved.
Vegetations may be single
or multiple, involve one or
more valve(s), differ in
appearance according to
the causative agent.
Infective Endocarditis:
Clinical features
 fever, fatigue, weight loss and chills.
 Cardiac murmurs.
 after 6 weeks: splenomegaly, petechiae, and clubbing of the fingers.
 Positive blood culture for the organisms (only minority of cases remain negative).
Complications:
 valve ulceration and perforation, rupture of chordae tendineae,
 arrhythmias, valvular regurgitation and congestive heart failure (due to destruction of a
valve).
 Septicemia or septic systemic embolization of infected vegetations which travel to multiple
sites, causing infarcts or abscesses in many organs (e.g. neurologic deficits due to
embolization to the brain or infarcts of the myocardium due to embolization to the
coronary artery),
 Pulmonary emboli is seen in tricuspid valve/ right sided endocarditis e.g. IV drug addicts.
 Mycotic/infected aneurysms of vessels.
 renal failure
 D. Gross photograph illustrating healed endocarditis with perforations on bicuspid aortic valve

Slide 13.43
Other types of endocarditis
1. Libman-Sacks endocarditis: Less common, non-infective,
verrucous endocarditis associated with elevated levels of
circulating immune complexes. Seen in patients with
systemic lupus erythematosus
2. Endocarditis of carcinoid syndrome: Secretory products
of carcinoid syndrome, especially 5-hydroxytryptamine
can cause endocarditis. The endocardial plaques are seen
in the right side of heart
3. Nonbacterial thrombotic endocarditis (marantic
endocarditis)
Nonbacterial Thrombotic Endocarditis
NBTE (marantic endocarditis)
 Characterized by sterile (no infection) vegetations (small
masses of fibrin, platelets, and other blood components) on the
leaflets of the cardiac valves. There is no infective organism. It is
aseptic.
 Pathogenesis/ association:
 Subtle endothelial abnormalities.
 Hypercoagulability.
 Association with malignancy (50%) and other debilitating
diseases.
Aortic valve most common site. The fibrin deposits are randomly
arranged.
May embolize to different parts of the body including brain, but the
emboli are sterile.
Diagrammatic comparison of the lesions in the four major forms of vegetative endocarditis. The
rheumatic fever phase of RHD (rheumatic heart disease) is marked by a row of warty, small
vegetations along the lines of closure of the valve leaflets. IE (infective endocarditis) is
characterized by large, irregular masses on the valve cusps that can extend onto the cords. NBTE
(nonbacterial thrombotic endocarditis) typically exhibits small, bland vegetations, usually attached
at the line of closure. One or many may be present. LSE (Libman-Sacks endocarditis) has small or
medium-sized vegetations on either or both sides of the valve leaflets.

Robbin and Cotran Pathology

Valvular Heart Disease
 Valvular Heart Disease
Two basic types:
1. Stenosis of valves: failure to open
2. Regurgitation of valves: Insufficiency or failure to close
Both cause murmurs
Causes
 Most common cause of acquired valvular heart disease is post
inflammatory scarring e.g. as a late complication of rheumatic fever or
secondary to various other inflammatory processes.
 may be congenital.
 can occur even with prosthetic cardiac valves
 can be secondary to thrombus formation or infectious endocarditis.
MITRAL VALVE
 Mitral valve
1. Mitral Valve Prolapse (picture)
 is the most frequent valvular lesion in developed
countries
 seen in young women.
 There is myxoid/mucoid degeneration of the valve
which causes ballooning of mitral valves (floppy
cusp), results in stretching of the mitral valve,
producing a parachute deformity of the cusp with
prolapse of the cusp into the atrium during
systole. These changes produce a characteristic
systolic murmur.
 Pathogenesis unknown
 Can be a component of Marfan syndrome
 Most patients asymptomatic but can occasionally
lead to mitral insufficiency and arrhythmias.
 Patients are predisposed to infective endocarditis.
 Mitral stenosis
 Stenosis is more common than regurgitation. Mitral stenosis is
most commonly due to rheumatic heart disease.
 In mitral stenosis (picture):
 Leaflets are thickened, fibrotic and fused leading to fish
mouth/button hole deformity (stenosed valve looks like fish's
mouth or button hole)
 Increased pressure, dilatation and hypertrophy of left
atrium.
 secondary deposition of Ca++
 Pulmonary hypertension and lungs are firm and heavy
(chronic passive congestion).
 Right heart may be affected later (right ventricular
hypertrophy).
Mitral regurgitation

Is usually due to rheumatic heart disease.

can also be due to mitral valve prolapse, infective
endocarditis, papillary muscle injury in myocardial
infarction etc.
Leads to left vent. hypertrophy and dilatation.
AORTIC VALVE
Aortic stenosis
Commonly caused by calcification and is
called as calcific aortic stenosis. Calcific aortic
stenosis affects:
a) Normal aortic valve as part of the aging
degenerative process in > 60 yrs old.
b) Congenital bicuspid aortic valve
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c) Valves scarred by rheumatic heart

disease
Aortic regurgitation/ insufficiency

can be caused by:

a) Non-dissecting aortic aneurysm.
b) Rheumatic heart disease
c) Infective endocarditis
d) Syphilitic (luetic) aortitis (rare)
Right side of heart

TRICUSPID VALVE
 Rarely involved in rheumatic heart disease.
And when involved it is along with the mitral
and aortic valves (not alone).
PULMONARY VALVE
 Can be affected in congenital malformations
e.g. tetralogy of Fallot.
 Is very rarely involved in rheumatic heart
disease