There is an estimated 10-15,000 new cases of IE diagnosed in the U.S. each year, although the exact incidence of IE is difficult to ascertain. IE is a relatively uncommon disease, is not a reportable disease, and different case definitions have existed throughout the years. Furthermore, the incidence varies greatly depending on geographic regions. IE is more common among males. The male:female ratio varies from 2:1 to 9:1 depending on the source. In the past, IE was a disease of children and young adults. It predominantly affected children with congenital heart disease and adults with rheumatic heart disease. Today, IE commonly affects the elderly, with almost 50% of cases in the U.S. occurring in patients over the age of 60. This may be due to the decreasing incidence of rheumatic heart disease and the increasing proportion of elderly in the U.S. Mortality from IE remains high, and ranges from 20-30% despite newer antibiotics and surgical options.
IE often occurs when there is an underlying cardiac abnormality that creates a high-low pressure gradient. The resultant turbulent blood flow disrupts the endocardial surface by peeling away the endothelium. The body’s natural response to endothelial damage is to repair it by laying down a sticky platelet-fibrin meshwork, which is a nidus for infection. Temporary bacteremia delivers the offending organism to the endocardial surface where is sticks to the platelet-fibrin meshwork. This festers into an infection that eventually invades the cardiac valves. The pathophysiology is slightly different with IVDA. It has been postulated that repeated injections of drugs and particulate material causes microtrauma to the cardiac valves, thereby starting the infection cascade.
Sometimes its difficult to see your way! Too easy – the patients fault self inflicted – the just desert of a lifetime of gluttony and sloth; or too difficult time consuming unrewarding Gps the gate keeper
Infective Endocarditis (IE): an infection of
the heart’s endocardial surface
The valves involved
› Mitral 28-45%
› Aortic 5-36%
› Both 0-35%
› Tricuspid 0-6%
› Pulmonary <1%
Incidence - varies according to location
Males > females
May occur at any age and increasingly
common in elderly
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
› Isolated secundum atrial septal defect
› ASD, VSD, or PDA > 6 months past repair
nfective Endocarditis: a changing disease
new high-risk subgroups
more difficult to prevent
more difficult to treat
1. Endocardium is resistant to
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
5. Eventual invasion of the valvular
Alteration of the valvular endothelial
surface leading to deposition of
platelets and fibrin
Bacteremia with seeding of non-
bacterial thrombotic vegetation
Adherence and growth, further
platelet and fibrin deposition
Extension to adjacent structures
› Papillary muscle, aortic valve ring abscess,
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
› Congenital abnormality (MV prolapse, bicuspid
› 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,
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.
Vegetations on valve closure lines
Destruction and perforation of valve
Rupture of chordae tendinae,
intraventricular septum, papillary
Valve ring abscess
› It has been found that 15% don’t have
murmurs at initial diagnosis, however most
develop a murmur during the course of the
› 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
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.
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.
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.
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.
Acute bacterial endocarditis caused by Staphylococcus aureus with perforation of
the aortic valve and aortic valve vegetations.
Acute bacterial endocarditis caused by Staphylococcus aureus with
aortic valve ring abscess extending into myocardium.
Bartonella henselae bacilli in cardiac valve of a patient with blood culture-
negative endocarditis The bacilli appear as black granulations.
S. Aureus mitral valve vegetation, anterior leaflet
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
› Petichiae (20-40%)
› Subcunjunctival and subungual splinter hemorrhages due
to lipid microembolism.
› Osler nodes
Tender, purplish erythematous papules in pulp of distal
Due to hypersensitive angitis – cultures are negative
› Janeway lesions
Erythematous, non-tender nodules on palms or soles.
› Clubbing found only in 10-20%.
› Roth spot- flame shaped hemorrhage occasionally takes
the form of cotton wool spot(rounded red with pale
Petechial rash. He was diagnosed with right-
sided staphylococcal endocarditis. Osler nodes
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.
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.
Roth spots: it has pale center and red periphery
› Immune complex mediated
glomerulonephritis (improve with effective
› 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
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
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,
› Affects normal
› Metastatic foci
› Commonly Staph.
› If not treated,
usually fatal within
› Often affects
› Indolent nature
› If not treated,
usually fatal by
The terms acute and subacute are used
to define duration of infection, however
are older terms and should not be used
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.
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
Renal emboli may cause flank pain and, rarely,
Splenic emboli may cause left upper quadrant
pain. Prolonged infection may cause
splenomegaly or clubbing of fingers and toes.
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.
Most patients with infective endocarditis should
respond within 48 hours of initiation of appropriate
If persistent fever consider:
perivalvular extension of infection and possible
Extracardiac embolic complications
Pulmonary embolism (secondary right-sided
endocarditis or prolonged hospitalization).
Drug reaction (the fever should promptly resolve after
Nosocomial infection (i.e. venous access site, urinary
ECG: Conduction abnormalities.
CBC: Normocytic normochromic
Urine exam: proteinurea and
microscopic hemeturia is common
› Relatively low sensitivity
› Good specificity
› Detection of valve ring abscess (87% vs. 28%
sensitivity for TTE)
› Detection of prosthetic valve IE especially in
› Detection of small vegetations (less than 2mm)
› Echocardiography cannot distinguish
• between infective and non infective
• Between vegetation, thrombus and pannus
• Between active and healed endocarditis
Limited thoracic windows = TTE low
Prior valvular abnormality
S. aureus bacteremia and suspected
Bacteremia with organisms likely to
= high prior probability of IE
MULTIPLE BLOOD CULTURES BEFORE
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
Not mandatory during the fever
Less common with improved blood culture
Prior antibiotic therapy(40%)
Fastidious(slowly growing organisms):
HACEK, Brucella, Bartonella, TropherymaWhipplei
Non bacterial organisms: Marantic, fungal
Special media required
› Brucella, Mycoplasma, Chlamydia, Histoplasma,
Longer incubation may be required
Coxiella burnetii (Q Fever), Trophyrema whipplei
will not grow in cell-free media(Serology)
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
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
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
Single positive blood culture for Coxeilla burnetti or phase IgG
antibody titer < 1 : 800
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
(abcess) , or
new partial dehiscence of prosthetic valve
2- New valvular regurgitation (New or changing of preexisting
1- Predisposition: predisposing heart condition or intravenous
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
Microorganisms demonstrated by histological examination of
a vegeation or intracardiac abcess or peripheral embolus
showing active endocarditis
Clinical criteria :
• Two major criteria, or
• One major and three minor criteria, or
• Five minor criteria
• One major and one minor criteria, or
• Three minor criteria
• Firm alternative diagnosis, or
• Resolution of IE syndrome (fever) ≥ 4 days of antibiotics, or
• No pathological evidence of IE at surgery or autopsy with
Noninfected (sterile) vegetation are caused
by non bacterial thrombotic endocarditis
The endocarditis of SLE called Libman-sacks
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
Histologically :they composed of bland
thrombi(Platelets+Fibrin, No bacteria or
inflammatory cells) that are loosely attached.
They are source of systemic emboli that
produce infarcts in brain,heart or
NBTE or marantic endocarditis also occur
in debilitated patient.
NBTE occur in DVT, mucinous
adenocarcinoma, is part of Trousseau
syndrome of migratory
Endocarditis of SLE ( Libman-Sacks
Disease). Mitral and tricuspid valvulitis
with small sterile vegetations.
over 0.5 cm
The valve is seen
on the left, and a
bland vegetation is
seen on the right. It
because it is
composed of fibrin
and platelets. It
displays about as
variation as a
brown paper bag.
typical of the non-
infective forms of
Here are flat, pale
the mitral valve
surface and even
on the chordae
Non infective Endocarditis (as in SLE,
Cardiac Neoplasms, Primary
Vegetations from pannus, thrombus
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
Blood tests to detect renal, hepatic,
hematological toxicity should be done
periodically (especially in 3rd
w. of therapy)
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.
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
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