A lecture on common problem infective endocarditis prepared by IslamGhanem Ahmed Ghanem assistant lecturer of cardiology Zagazig university 2013

6.  Infective Endocarditis (IE): an infection of
the heart’s endocardial surface

9.  The valves involved
› Mitral 28-45%
› Aortic 5-36%
› Both 0-35%
› Tricuspid 0-6%
› Pulmonary <1%

11.  Incidence - varies according to location
 Males > females
 May occur at any age and increasingly
common in elderly
 Mortality 20-30%
 Decline in incidence of rheumatic fever
 The commonest cause in adults is mitral
valve prolapse with regurgitation
 More prosthetic valves
 More nosocomial cases, injected drug use
 More staphylococcal infection

12.  Native IE:
 Streptococcus viridnas
 Streptococcus bovis
 Staphylococcus
aureus
 Staphylococcus
epidermidis
 HACEK organisms
 Prosthetic IE:
 Early (>1year)
 Staphylococcus
epidermidis
 Staphylococcus
aureus
 Streptococcus viridnas
 Enerococci
 Late(<1year)
 As native IE

13.  Haemophilus aphrophilus, H.
paraphrophilus, parainfluenzae
 Actinobacillus actinomycetemcomitans
 Cardiobacterium hominis
 Eikenella corrodens
 Kingella kingae

15.  High risk
› MVP with regurgitaion
› Prosthetic cardiac valve
› Prior episodes of endocarditis
› Degenerative valvular diseases
› Complex congenital cardiac defect
› Surgical systemic-pulmonary shunts
– Intravenous drug abuse
– Intravascular catheters

16.  Moderate risk
› PDA, VSD, primum ASD
› Co-Aorta
› Bicuspid aortic valve
› Hypertrophic cardiomyopathy

17.  Low risk
› Isolated secundum atrial septal defect
› ASD, VSD, or PDA > 6 months past repair

18. nfective Endocarditis: a changing disease
new high-risk subgroups
IVDA
elderly
intracardiac devices
nosocomial diseases
more difficult to prevent
more difficult to treat

20. 1. Endocardium is resistant to
infection
2. Turbulent blood flow disrupts the
endocardium making it “sticky”
3. Bacteremia delivers the organisms
to the endocardial surface
4. Adherence of the organisms to the
endocardial surface
5. Eventual invasion of the valvular
leaflets

21.  Alteration of the valvular endothelial
surface leading to deposition of
platelets and fibrin
 Bacteremia with seeding of non-
bacterial thrombotic vegetation
(NBTE)
 Adherence and growth, further
platelet and fibrin deposition
 Extension to adjacent structures
› Papillary muscle, aortic valve ring abscess,
conduction system

22.  Low pressure side of structural lesion
› Atrial side of mitral valve (MR)
› Ventricular side of aortic valve (AR, AS with R)
› But, Non infective endocarditis vegetations occur
at atrial side of mitral valve, aortic side of aortic
valve
› Congenital abnormality (MV prolapse, bicuspid
AV)
› Scarring from rheumatic heart disease or sclerosis
as a consequence of aging
› Prosthetic valves
 Other turbulence, high-velocity jets
› Ventricular septal defect
› Stenotic valve
 Direct mechanical damage from catheters,
pacemaker leads

23. The clinical manifestation IE result from:
1. The local destructive effects of intracardial infection;
2. The embolization of septic fragments of vegetations
to distant sites, resulting in infarction or infection;
3. The hematogenous seeding of remote sites during
continuous bacteremia and
4. An antibody response to the infecting organism with
subsequent tissue injury due to deposition of
preformed immune complexes.

24.  Vegetations on valve closure lines
 Destruction and perforation of valve
leaflet
 Rupture of chordae tendinae,
intraventricular septum, papillary
muscles
 Valve ring abscess
 Myocardial abscess
 Conduction abnormalities

25.  Heart murmurs
› It has been found that 15% don’t have
murmurs at initial diagnosis, however most
develop a murmur during the course of the
disease
› Changing murmurs – factors other than
valvular integrity like change in cardiac
output, temperature, hematocrit may play a
role. However new onset regurgitant murmur
in a setting of acute sepsis is virtually
diagnostic.

26. MORPHOLOGY
 The hallmark of IE is presence of friable, bulky, potentially
destructive vegetations containing fibrin, inflammatory cells and
bacteria or other organisms.
 Aortic and mitral valve most common sites, valves of right heart
may be involved particularly in intravenous drug abusers.
 Vegetations sometimes erode into the underlying myocardium
and produce an abscess (ring abscess).
 Emboli may shed from the vegetation leading to abscesses
formation at the site where emboli lodged, this may lead to
sequelae such as septic infracts or mycotic aneurysms.
 The vegetations of subacute endocarditis are associated with
less valvular destruction than acute endocarditis.
 Microscopically vegetations of typical subacute IE often have
granulation tissue indicating healing at the bases.
 With time fibrosis, calcification and a chronic inflammatory
infiltrate can develop.

33. The aortic valve with a large,
irregular, reddish tan vegetation
Here, infective endocarditis on the
mitral valve has spread into the septum
all the way to the tricuspid valve,
producing a fistula.

34. Microscopically, the valve in infective endocarditis demonstrates friable
vegetations of fibrin and platelets (pink) mixed with inflammatory cells and
bacterial colonies (blue). The friability explains how portions of the vegetation
can break off and embolize.

35. Here is a valve with infective endocarditis. The blue bacterial colonies on the lower
left are extending into the pink connective tissue of the valve. Valves are relatively
avascular, so high dose antibiotic therapy is needed to eradicate the infection.

36. Acute bacterial endocarditis caused by Staphylococcus aureus with perforation of
the aortic valve and aortic valve vegetations.

37. Acute bacterial endocarditis caused by Staphylococcus aureus with
aortic valve ring abscess extending into myocardium.

38. Bartonella henselae bacilli in cardiac valve of a patient with blood culture-
negative endocarditis The bacilli appear as black granulations.

39. S. Aureus mitral valve vegetation, anterior leaflet

41.  Systemic embolism is reported to occur
in over 50% cases in autopsy studies.
 Most common sites are brain, kidneys,
skin, spleen, eye and CNS (coronary
embolization is rare).
 There is increasing evidence to show that
embolic phenomena actually represent
“immune complex” deposition in small
systemic arteries.

42.  Cutaneous manifestations
› Petichiae (20-40%)
› Subcunjunctival and subungual splinter hemorrhages due
to lipid microembolism.
› Osler nodes
 Tender, purplish erythematous papules in pulp of distal
fingers
 Due to hypersensitive angitis – cultures are negative
› Janeway lesions
 Erythematous, non-tender nodules on palms or soles.
› Clubbing found only in 10-20%.
 Ocular manifestations
› Roth spot- flame shaped hemorrhage occasionally takes
the form of cotton wool spot(rounded red with pale
center).

44. Janeway lesions
Splinter
hemorrhages
Osler node

48. Petechial rash. He was diagnosed with right-
sided staphylococcal endocarditis. Osler nodes

49. Osler's nodes on a finger and foot.
Janeway lesions are Flat, painless,
erythematous lesions seen on the palm
of this patient's hand. Frequently
associated with bacterial endocarditis.

52. Seen here in the finger at the right are small splinter hemorrhages in a patient
with infective endocarditis. These hemorrhages are subungual, linear, dark red
streaks. Similar hemorrhages can also appear with trauma.

53. Roth spots: it has pale center and red periphery

57.  Renal
› Immune complex mediated
glomerulonephritis (improve with effective
antibiotics)
› Focal glomerulonephritis and embolic renal
infarct manifest with hematuria but rarely
leading to renal failure
› Renal failure is mostly due to impaired
hemodynamics, antibiotics toxicity
 Splenic enlargement, infarction
 Septic or bland pulmonary embolism

59.  Neurological (mostly Staph.aureus)
› Embolic stroke is the commonest (Antibiotic is the
anticoagulant in this case, Thrombolytics and
anticoagulants are relatively contraindicated)
› Intracranial hemorrhage (rupture of mycotic
aneurysm, septic arteritis, hemorrhage into an
infarct)
 Mycotic aneurysm: Focal dilatations of arteries
occuring at points in the arterial wall that have been
weakened by infection in the vasa vasorum or where
septic emboli have lodged.
› Encephalopathy,cerebritis, brain abcesses,
meninigitis

65.  Acute
› Affects normal
heart valves
› Rapidly
destructive
› Metastatic foci
› Commonly Staph.
› If not treated,
usually fatal within
6 weeks
 Subacute
› Often affects
damaged heart
valves
› Indolent nature
› If not treated,
usually fatal by
one year

66.  The terms acute and subacute are used
to define duration of infection, however
are older terms and should not be used

74.  Symptoms
› Fever, sweats, chills
› Anorexia, malaise, weight loss
 Signs
› Anemia (normochromic, normocytic)
› Splenomegaly
› Microscopic hematuria, proteinuria
› New or changing heart murmur, CHF
› Embolic or immunologic dermatologic signs
› Hypergammaglobulinemia, elevated ESR,
CRP, RF

76. SYMPTOM AND SIGNS
SBE: Initially, symptoms are vague: low-grade fever (<
39° C), night sweats, fatigability, malaise, and weight
loss. Chills and arthralgias may occur. Symptoms and
signs of valvular insufficiency may be a first clue.
Initially, ≤ 15% of patients have fever or a murmur, but
eventually almost all develop both. Physical
examination may be normal or include pallor, fever,
change in a preexisting murmur or development of a
new regurgitant murmur, and tachycardia.
 Retinal emboli can cause round or oval hemorrhagic
retinal lesions with small white centers (Roth's spots).
 Cutaneous manifestations include petechiae (on the
upper trunk, conjunctivae, mucous membranes, and
distal extremities), painful erythematous subcutaneous
nodules on the tips of digits (Osler's nodes), nontender
hemorrhagic macules on the palms or soles (Janeway
lesions), and splinter hemorrhages under the nails.

77.  About 35% of patients have CNS effects,
including transient ischemic attacks, stroke, toxic
encephalopathy, and, if a mycotic CNS aneurysm
ruptures, brain abscess and subarachnoid
hemorrhage.
 Renal emboli may cause flank pain and, rarely,
gross hematuria.
 Splenic emboli may cause left upper quadrant
pain. Prolonged infection may cause
splenomegaly or clubbing of fingers and toes.

78.  ABE and PVE: Symptoms and signs are
similar to those of SBE, but the course is
more rapid. Fever is almost always present
initially, and patients appear toxic;
sometimes septic shock develops. Heart
murmur is present initially in about 50 to
80% and eventually in > 90%. Rarely,
purulent meningitis occurs.
 Right-sided endocarditis: Septic pulmonary
emboli may cause cough, pleuritic chest
pain, and sometimes hemoptysis. A
murmur of tricuspid regurgitation is typical.

79.  Congestive heart failure
 Extravalvular cardiac manifestations
( myocarditis, conduction disturbances)
 Systemic and pulmonary embolism
 Mycotic aneurysm
 Neurologic – stroke, neuropsychiatric
syndromes
 Renal – glomerulonephritis, renal infarcts
 Hematological – anemia, TTP

81.  Most patients with infective endocarditis should
respond within 48 hours of initiation of appropriate
antibiotic therapy.
If persistent fever consider:
 perivalvular extension of infection and possible
abscess formation.
 Extracardiac embolic complications
 Pulmonary embolism (secondary right-sided
endocarditis or prolonged hospitalization).
 Drug reaction (the fever should promptly resolve after
drug withdrawal)
 Nosocomial infection (i.e. venous access site, urinary
tract infection)

85.  Echocardiography: esp
transesophageal echocardiography.
 Blood culture.
 Serology(Immunoglobulins and
compliment).
 ECG: Conduction abnormalities.
 CBC: Normocytic normochromic
anemia, leukocytosis.
 ESR.
 Urine exam: proteinurea and
microscopic hemeturia is common

86.  Transthoracic
› Relatively low sensitivity
› Good specificity
 Transesophageal
› Detection of valve ring abscess (87% vs. 28%
sensitivity for TTE)
› Detection of prosthetic valve IE especially in
mitral position
› Detection of small vegetations (less than 2mm)
› Echocardiography cannot distinguish
• between infective and non infective
vegetations
• Between vegetation, thrombus and pannus
• Between active and healed endocarditis

87.  Limited thoracic windows = TTE low
sensitivity
 Prosthetic valves
 Prior valvular abnormality
 S. aureus bacteremia and suspected
IE
 Bacteremia with organisms likely to
cause IE
= high prior probability of IE

95. mitral valve vegetation

103.  MULTIPLE BLOOD CULTURES BEFORE
EMPIRIC THERAPY
 If not critically ill
› 3 blood cultures over 12-24 hour period
› ? Delay therapy until diagnosis confirmed
 If critically ill
› 3 blood cultures over one hour
 20 cm each sample from 3 different
puncture sites
 Not mandatory during the fever

104.  Less common with improved blood culture
methods
 Causes:
 Prior antibiotic therapy(40%)
 Fastidious(slowly growing organisms):
HACEK, Brucella, Bartonella, TropherymaWhipplei
 Non bacterial organisms: Marantic, fungal
endocarditis
 Special media required
› Brucella, Mycoplasma, Chlamydia, Histoplasma,
Legionella, Bartonella
 Longer incubation may be required
› HACEK
 Coxiella burnetii (Q Fever), Trophyrema whipplei
will not grow in cell-free media(Serology)

107.  Electrocardiogram
› Conduction delays
› Ischemia or infarction (coronary embolism)
 Chest X-ray
› Septic emboli in right-sided IE
› Valve calcification (degenerative heart
disease)
› CHF

108.  PCR
› Coxiella burnetii
› Tropheryma whipplei
› Bartonella henselae
 Serology
› Coxiella burnetii
› Bartonella
› Brucella
› Legionella
› Chlamydophila psittaci

109.  1977 Pelletier and Petersdorf criteria
 1981 von Reyn criteria
 1994 Duke criteria
 2000 Modified Duke criteria: It is of limited
value in PVE, CDRIE, BCNIE and should
not replace the clinical judgment

110.  Major criteria:
 A. Positive blood culture for Infective Endocarditis
1- Typical microorganism consistent with IE from 2 separate blood
cultures, as noted below:
viridans streptococci, Streptococcus bovis, or HACEK group, or
community-acquired Staphylococcus aureus or enterococci, in
the absence of a primary focus
 or
2- Microorganisms consistent with IE from persistently positive blood
cultures defined as:
 2 positive cultures of blood samples drawn >12 hours apart, or
 all of 3 or a majority of 4 separate cultures of blood (with first and
last sample drawn 1 hour apart)(Persistntly +ve blood cultures
The best)
 Single positive blood culture for Coxeilla burnetti or phase IgG
antibody titer < 1 : 800

111.  B. Evidence of endocardial involvement
1- Positive echocardiogram for IE defined as :
 (vegetation) oscillating intracardiac mass on valve or
supporting structures, in the path of regurgitant jets, or on
implanted material in the absence of an alternative anatomic
explanation, or
 (abcess) , or
 new partial dehiscence of prosthetic valve
2- New valvular regurgitation (New or changing of preexisting
murmur)

112.  Minor criteria:
1- Predisposition: predisposing heart condition or intravenous
drug use
2- Fever: temperature > 38.0° C (100.4° F)
3- Vascular phenomena: major arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage,
conjunctival hemorrhages, and Janeway lesions
4- Immunologic phenomena: glomerulonephritis, Osler's nodes,
Roth spots, and rheumatoid factor
5- Microbiological evidence: positive blood culture but does not
meet a major criterion as noted above or serological
evidence of active infection with organism consistent with IE

113.  Diagnosis
 Definite:
 Pathological criteria:
Microorganisms demonstrated by histological examination of
a vegeation or intracardiac abcess or peripheral embolus
showing active endocarditis
 Clinical criteria :
 Definite:
• Two major criteria, or
• One major and three minor criteria, or
• Five minor criteria
 Possible:
• One major and one minor criteria, or
• Three minor criteria
 Rejected:
• Firm alternative diagnosis, or
• Resolution of IE syndrome (fever) ≥ 4 days of antibiotics, or
• No pathological evidence of IE at surgery or autopsy with

117.  Noninfected (sterile) vegetation are caused
by non bacterial thrombotic endocarditis
 The endocarditis of SLE called Libman-sacks
endocarditis.
 NBTE is characterized by deposition of small
sterile thrombi on the leaflet of cardiac valve
 Grossly the lesions are 1mm-5mm in size occur
singly on the line of closure of leaflets (at
atrial side of mitral valve, aortic side of
aortic valve).
 Histologically :they composed of bland
thrombi(Platelets+Fibrin, No bacteria or
inflammatory cells) that are loosely attached.

118.  They are source of systemic emboli that
produce infarcts in brain,heart or
elsewhere.
 NBTE or marantic endocarditis also occur
in debilitated patient.
 NBTE occur in DVT, mucinous
adenocarcinoma, is part of Trousseau
syndrome of migratory
thrombophelebitis.
 Endocarditis of SLE ( Libman-Sacks
Disease). Mitral and tricuspid valvulitis
with small sterile vegetations.

119. 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.

120. 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.

121. Libman-sacks
endocarditis.
Here are flat, pale
tan, spreading
vegetations over
the mitral valve
surface and even
on the chordae
tendineae.

122.  Non infective Endocarditis (as in SLE,
Antiphospholipid Syndrome)
 Cardiac Neoplasms, Primary
 Vegetations from pannus, thrombus

134.  Resolution of fever within 5-7 days
 Blood culture become sterile within 2 days
(Except in Staph. up to 9 days)
 Blood culture should be repeated daily until
sterile, rechecked if recrudescent fever ,
performed again 4-6 weeks after therapy to
document cure
 Blood tests to detect renal, hepatic,
hematological toxicity should be done
periodically (especially in 3rd
w. of therapy)

138.  Emergent: Within 24h.
 Urgent: Within few days.
 Elective: After 1-2w.of antibiotics.
 If there is indication for surgery&
 Cerebral hemorrhage: Postpone for 4w.
 Cerebral infarction: Postpone for 2w.

144.  Use ampho B and flucytosine ( toxic to B.
marrow and kidneys)
 Almost always needs surgery .
 Long term oral prophylaxis is often given
to prevent relapse

145. 513 patients with complicated IE , 230 (40%) surgical therapy513 patients with complicated IE , 230 (40%) surgical therapy
6 month mortality6 month mortality
Impact of surgery on mortalityImpact of surgery on mortality