Endocarditis

1
Endocarditis
2
Epidemiology
An estimated 10,000 to 15,000 new cases of
infective endocarditis (IE) are diagnosed in the
United States each year. Men predominate in
most case series, with male-to-female ratios
ranging from 21 to 91. The importance of
underlying heart disease in children with IE
varies with age 50 to 70 percent of children
less than 2 years old have no obvious underlying
cardiac disease , while most older children have
coexistent congenital heart disease. A number of
factors predispose to the development of
infective endocarditis. These include IVDA,
prosthetic heart valves, and structural heart
disease.
3
Newer trends show endocarditis has increasingly
become a disease of the elderly. This trend is
probably due to the decline in the incidence and
importance of rheumatic heart disease as a risk
factor for IE and the increasing proportion of
elderly subjects in the general population. Also
the proportion of cases that present with an
indolent course and the proportion due to
streptococci has declined recently, while
simultaneous increases have occurred in the
proportion of cases due to Staphylococcus aureus,
fungi, and gram negative bacilli. The rising
incidence of injection drug use (IVDA) has had an
impact on the overall incidence of endocarditis,
as well as its geographic distribution. Drug
addiction as a cause of IE is most prominent in
patients less than 40 years old.
4
Intravenous Drug Abuse (IVDA)
In addition to the injection itself, specific
drugs of abuse may also be risk factors for the
development of endocarditis which often involves
the right side of the heart. One large study
found that those who used cocaine were
significantly more likely to have endocarditis
than those using other drugs. Ann Int Med 1987.
106833. The most significant risk factor for
right-sided IE is IVDA however, left-sided
disease may be more common in addicts. The most
common infecting organism is S. aureus,
particularly in right-sided infection with
prevalence up to 82 percent. The vegetations are
usually or 1 cm in diameter, and there is a
marked increase in mortality associated with
vegetations greater than 2 cm (33 versus 1.3
percent for smaller vegetations). Ann Int Med
1992. 117560.
5
Prosthetic Heart Valve
Prosthetic valve endocarditis develops in 1 to 4
percent of valve recipients during the first year
following valve replacement, and in approximately
0.5-1 percent per year thereafter. The type of
prosthetic valve (bio vs mech) does not have an
impact on the development of IE.
6
Structural Heart Disease
Approximately 3/4 of all patients with IE have a
preexisting structural cardiac abnormality at the
time that endocarditis begins. The risk of IE in
patients with mitral valve prolapse and
associated regurgitation is estimated to be 5 to
8 times higher than that in the normal
population. However, MVP without MR is a more
common abnormality that is associated with only a
small risk of endocarditis. NEJM 1982. 307776.
The most common predisposing congenital heart
lesions are bicuspid aortic valves, patent ductus
arteriosus, ventricular septal defect,
coarctation of the aorta, and tetralogy of
Fallot. Prevalence of rheumatic valve disease is
on the decline.
7

• The risk of IE appears to be dependent upon the
  specific congenital or acquired cardiac lesion.
  One study, for example, evaluated 2401 patients
  with congenital heart lesions who were followed
  prospectively for 40,000 days. Circulation 1993.
  87 121
• The overall incidence of endocarditis was
  135 cases/100,000 person years.
• The highest rates of endocarditis occurred
  in patients with aortic stenosis (271)and
  ventricular septal defects (145 cases/100,000
  person yrs).
• Among patients with AS, the higher the peak
  gradient, the higher the risk of developing
  endocarditis.
• The risk of IE with AS was approximately twice
  as high as with aortic regurgitation.
• The lowest rate of endocarditis occurred with
  pulmonic stenosis.
• The risk of IE also appears to be very low in
  adults with congenital heart disease, inherently
  normal pulmonic and tricuspid valves, and
  pulmonary or tricuspid regurgitation due to
  pulmonary hypertension.

8
Other Risk factors
A prior history of endocarditis is an important
predisposing cause for IE. Recurrent endocarditis
occurred in 4.5 percent of one large cohort of
non-addicts who survived their initial episode.
Ann Int Med 1992 117567. A number of cases of
IE have been reported in patients with HIV
infection with some valves have been infected
with unusual organisms such as Salmonella and
Listeria. It has been suggested that HIV
infection is an independent risk factor for IE in
injection drug abusers but, this has not been
confirmed in other reports. Other less common
predisposing factors for IE are pregnancy,
arteriovenous fistulas used for hemodialysis,
central venous and pulmonary artery catheters,
peritoneovenous shunts for the control of
intractable ascites and ventriculoatrial shunts
for the management of hydrocephalus.
9
Patients with ulcerative lesions of the colon due
to carcinoma or inflammatory bowel disease have a
poorly understood predilection to develop
endocarditis secondary to Streptococcus bovis.
IE has also been reported in patients
undergoing liver, heart, and heart-lung
transplantation.
10
Pathogenesis
The endothelial lining of the heart and its
valves is normally resistant to infection with
bacteria and fungi. Although a few highly
virulent organisms such as Staphylococcus aureus
are capable of infecting normal human heart
valves, the initial step in the establishment of
a vegetation is injury to the endocardium,
followed by focal adherence of platelets and
fibrin. These injuries can probably occur
naturally in bacteremic humans with congenital or
acquired cardiac lesions that induce continuous
endocardial trauma via regurgitant flow or high
pressure jets of blood through stenotic
lesions. The initially sterile platelet-fibrin
nidus then becomes infected by microorganisms
circulating in the bloodstream, following
colonization then microbial growth results in the
secondary accumulation of more platelets and
fibrin.
11
Microbial adherence is a crucial early event in
the pathogenesis of endocarditis. As an example,
bacteria that are typically found in patients
with endocarditis, such as Staphylococcus aureus,
viridans streptococci, enterococci and P.
aeruginosa, adhere more avidly to excised canine
heart valves in vitro than species which rarely
cause endocarditis (such as Escherichia
coli). Dextran in the cell wall of gram positive
organisms is one factor. Degree of intrinsic
binding affinity to fibronectin is important in
the virulence of S. aureus species.
12
Components found in damaged endothelium and/or
platelet-fibrin aggregates that may mediate
adherence include fibrinogen, laminin, and type 4
collagen. Animals treated with aspirin had
reduction in the weight of valvular vegetations,
vegetation growth, density of bacteria in the
kidneys and in vegetations, and a decrease in
embolic events compared to controls. This
interference with platelet-fibrin aggregates
suggests that addition of low dose aspirin can
reduce risk of embolization during antibiotic
treatment, or risk of IE recurrence. A small
clinical study of 9 pts suggested ASA to be
protective.

J Int Med 1992 231543
13
However a more recent randomized trial showed
despite promising experimental data, there was no
clinical benefit to ASA. 115 pts in CanUS were
doubly blinded to receive ASA or
placebo. Followed for 4wks for primary outcome of
clinical embolism, secondary outcome of CT shown
subclinical CVA, hemorrhage or death. No sig
difference in embolization. (ASA 28 vs placebo
20) Non-sig trend for combined majorminor
hemorrhage in ASA grp. Total of 70 had CT head
done, with significant lesions in 39.5 ASA group
vs 29.3 in placebo. Total of 42 had TEE, which
showed similar rate of vegetation decrease or
valvular regurgitation.
JACC 2003 42775
14
Physics of Vegetations
If nebulized Serratia marcescens, are injected
into an air stream passing through an agar-coated
Venturi tube, the highest concentration of
bacteria is found in the low pressure area
immediately distal to the narrowing. Circulation
1963. 2718 Vegetations in patients with
preexisting valvular lesions are usually located
on the atrial surface of incompetent
atrioventricular valves, or the ventricular
surfaces of incompetent semilunar
valves. Patients with ventricular septal defects
tend to develop vegetations on the orifice of the
defect, on the right ventricular side of the
opening, and secondarily on the tricuspid and
pulmonic valves. Vegetations may occasionally
localize on the chordae tendineae of the anterior
leaflet of the mitral valve in patients with
aortic insufficiency. Patients with mitral
regurgitation may develop vegetations
(MacCallum's patch) on the wall of the left
atrium where the regurgitant jet strikes the
atrial wall and results in endocardial thickening.
15
Clinical Sequelae
Vegetations often prevent proper valvular leaflet
or cusp coaptation, thereby causing valvular
incompetence. Congestive heart failure may
result from worsening valvular incompetence or
leaflet perforation secondary to vegetation
growth. Patients with mitral or tricuspid valve
vegetations may develop chordal
rupture. Infection may also extend into
surrounding structures such as the valve ring,
the adjacent myocardium, the cardiac conduction
system, or the mitral-aortic intravalvular
fibrosa. Rarely, cavitation of periaortic
abscesses occurs into the adjacent aortic wall,
resulting in the formation of a diverticulum or
aneurysm. Even more rarely, such aneurysms
perforate into surrounding structures, resulting
in aortic-atrial or aortic-pericardial fistulae.
16
Etiology (Native Valve)
Although any bacteria can cause IE, Streptococci,
Enterococci and Staphylococci account for the
majority of the cases. Streptococci Streptococci
account for about 55 of non-IVDA
cases. Viridans streptococci account for 75 of
these cases. Most common of the group are
Streptococcus mutans, S. mitis, S. Milleri. S.
Bovis account for 20. Other Streptococci are
5. Viridans strep are normal pharynx
inhabitants and are generally very susceptible
to PCN. 80 of S. Bovis cases occurs in elderly
(60yrs). More than a third have a malignant or
pre-malignant colonic lesion.
17
Enterococci Cause about 6 of native valve
endocarditis and are normal flora of GI tract,
anterior urethra and occasionally the
mouth. They are relatively resistant to PCN-G
and require the addition of an aminoglycoside to
achieve bactericidal effect. More common among
males who develop infection around 60 yrs of
age. Many have history of GU tract manipulation,
trauma or disease. Cystoscopy, Foley catheter,
prostatectomy. Caesarian section, abortion,
pregnancy.
18
Staphylococci Staph cause about 30 of native
valve IE cases, with S. aureus being 5 to 10
times more frequent than S. epidermidis. S.
Aureus can rapidly attack normal or damaged
valves. It has a fulminant course with death
from bacteremia within days, or from heart
failure within weeks. Abscesses are common at
multiple sites. S. Epidermidis usually infects
prosthetic valves.
19
HACEK organisms Haemophilus Actinobacillus Cardio
bacterium Eikenella Kingella They are part of
the oropharyngeal flora and produce large
vegetations with a subacute presentation. They
are difficult to isolate from blood and grow
slowly in blood culture media. Incubation for 7
to 14 days may be required to detect their
growth. This delayed growth makes standard
antibiotic susceptibility testing difficult.
20
Other Bacteria Almost any bacteria can be an
occasional cause of acute or subacute
endocarditis. Streptococcus pneumoniae Neisseria
gonorrhoeae Enteric gram ve bacilli Pseudomonas S
almonella Streptobacillus Serratia
marcescens Bacteroides Brucella Mycobacterium Neis
seria meningitidis Listeria Legionella Corynebacte
rium
21
Fungi Rarely cause native valve IE. Subacute
course with large vegetations and large
emboli. Candida and Aspergillus species can
occur in persons with intravascular catheters who
are frequently on glucocorticoids, broad
spectrum Abx, cytotoxic drugs. Grave prognosis
due to the relatively poor activity of
antifungal agents. Other Organisms Rare causes
can include Spirochetes, Rickettsiae (Coxiella
burnetti), Chlamydiae (C. pneumoniae, C.
trachomatis, C. psittaci).
22
Etiology (IVDA)
Frequently occurs in young males with the skin
being the most common source of organisms.
Contamination of drugs is less common. More than
50 is by S. aureus. 20 by Streptococci and
Enterococci. 6 Fungi, mainly candida. 6
gram ve bacilli, usually Pseudomonas
species. Onset is usually acute, with only 20
of addicts having previously damaged valves.
Half the cases are involving the tricuspid
valve. Aorta is involved in 25 of cases. Mitral
valve is involved 20 of the time. Multiple
valves less than 5. In TV endocarditis, murmurs
are usually absent and pneumoniae from septic
emboli is frequently the presenting picture.
23
Etiology (Prosthetic Valve)
With the aging population, prosthetic valve
endocarditis now accounts for 10 to 20 of
cases. Intravascular sutures, pacemaker wires
and Teflon-Silastic tubes are all foci for
infection. Most patients are males over 60 and
IE occurs in 1-2 in the first year after surgery
, and 0.5 a year thereafter. AV prosthesis are
more likely to be involved than MV, and infection
is usually at the suture line. Early onset
(within 60days) is usually as a result of valve
contamination or peri-operative bacteremia.
24
Almost half of early onset, and third of late
onset endocarditis are due to Staphylococci. S.
epidermidis is more frequently involved than S.
aureus. Streptococci are the most common cause
(40) of late onset endocarditis, but are rare in
early onset.
25
Clinical Manifestations
Symptoms generally start within two weeks of
precipitating event. With low pathogenicity
organism (ie viridans)the onset is usually slow
with low fevers. With fulminant disease (ie S.
aureus) the onset is rapid with high
fevers. Fever is almost always present.
Arthralgias, myalgias and low back pain are
common. Cardiac murmurs are almost always
present, except in acute early IE and in IVDA
with TV lesions. Splenomegaly and petechia are
usually found in disease of long
duration. Petechiae are more common on
conjunctiva, palate, buccal mucosa and upper
extremities.
26
Splinter hemorrhages are subungual, linear dark
red streaks that may appear in IE, but can also
result from trauma. Roths spots are oval
retinal hemorrhages with a clear pale center. But
it can occur in connective tissue diseases and
sever anemia. Oslers nodes are small tender
nodules in the pads of fingers and
toes. Janeways lesions are small circular
hemorrhagic lesions, that are nodular and occur
on palms and soles of feet. Clubbing has been
reported in patients with long standing
disease. Embolic episodes can occur during or
after therapy. Large emboli are generaly fungal.
27
Neurologic manifestations are more common in left
sided disease, and in S. aureus infection. Heart
failure can occur long after its cure. Causes
include valvular damage, myocarditis, abscess
formation and coronary artery embolization with
infarction. Conduction defects occur due to
septal invasion. Renal disease exists in most
patients due to renal emboli, or immune complex
mediated glomerulonephritis.
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Diagnostic Workup
At least three blood cultures should be obtained
from separate sites over a time period ranging
from a few hours to one to two days depending
upon the severity of illness and urgency of the
need for treatment. The additional diagnostic
yield of more than three cultures is minimal in
patients who have not recently received
antimicrobial therapy.
34
A TTE should initially be obtained in patients
with native heart valves, while those with
prosthetic valves should undergo TEE. Detection
of a vegetation is a positive test. However, this
procedure has relatively low sensitivity in IE.
Thus, a negative study does not preclude the
diagnosis TTE should be followed by TEE, which
has higher spatial resolution, when there is an
intermediate or high suspicion of IE and valvular
abnormalities were found on TTE. In general the
sensitivity of TTE in detecting vegetations is
65-80. The addition of TEE increases the
sensitivity to 95. In prosthetic valves TTE is
has poor diagnostic value. However, TEE carries a
90 sensitivity in this setting.


JACC
199118
35
A meticulous clinical examination should be
performed looking for clinical evidence of small
and large emboli with special attention to the
fundi, conjunctivae, skin, and digits. In
addition, a careful cardiac examination may
reveal signs of new regurgitant murmurs and signs
of congestive heart failure, and neurologic
evaluation may detect evidence of focal
neurologic impairment and can be used to document
a baseline should such abnormalities appear
later.
36
Additional clues to the presence of IE, such as
microscopic hematuria, leukocytosis, and evidence
of renal impairment should be sought with
laboratory testing. All patients with suspected
IE should have an electrocardiogram to determine
whether there is evidence of heart block or a
conduction delay and to establish a baseline
should such a complication develop later.
37
Echo Samples
38
Duke Classification
In 1994 investigators from Duke University
modified the von Reyn criteria to include the
role of echocardiography in diagnosis. They also
expanded the category of predisposing heart
conditions to include injection drug use. This
was later modified further to include the role of
TEE as well as the agent of Q fever (Coxiella
brunetti). The Duke classification relies upon
major and minor criteria in a manner similar to
the Jones criteria for rheumatic fever.
39

• Major Criteria
• Isolation of causative organism by two separate
  blood cultures at least 12hrs apart.
• Endocardial involvement evidence by echo.
  Oscillating mass, prosthetic valve dehiscence,
  abscess, new regurgitation.
• Minor criteria
• Predisposing lesion or IVDA
• Fever 38C
• Signs of embolization Janeway lesion, Intracran
  hem.
• Immunologic phenomena Glomerulonephritis, Oslers
  nodes, Rheumatoid factor, Roths spots.
• Positive blood culture not meeting major
  criteria.
• Echo finding, but not meeting major criteria.

40
Modified Duke Criteria Definite Infective
Endocarditis Pathologic criteria Microorganisms
demonstrated by culture or histology in a
vegetation or embolus. Clinical criteria 2
major or 1 major 3 minor or 5 minor Possible
endocarditis Findings that are suggestive of IE
but fall short of definite, but not
rejected. Rejected Infective Endocarditis Alterna
te diagnosis explaining evidence of
endocarditis Resolution of syndrome with
antibiotic therapy in 4 days or less. No
pathologic evidence at surgery with Abx therapy
of four days or less.
Clin Inf Dis 200030
41
Treatment Regimens
In general the antibiotic regimen chosen is based
on agent isolated. The initial microbiologic
response to therapy should be assessed by
obtaining repeat blood cultures 48 to 72 hours
after antibiotics are begun. Most patients with
IE generally become afebrile three to five days
after treatment is begun with an appropriate
antibiotic. Patients with Staphylococcal aureus
endocarditis may respond somewhat more slowly,
remaining febrile for five to seven days after
the institution of therapy. In general, oral
regimens should not be used as initial therapy,
but may be used in highly selected cases. In
right-sided endocarditis of IVDA combination oral
therapy with rifampin and ciprofloxacin was as
effective as parenteral therapy in patients in
whom oral therapy could be closely supervised. Am
J Med 1996.10168
42
Treatment regimen summary Native valve Strep
Viridans or Strep Bovis -PCN sensitive PCN-G or
Ceftriaxone 4wks If allergic, Vancomycin
4wks Strep Viridans or Strep Bovis - PCN
resistant PCN 4wksGent 2wk Vancomycin
4wks Enterococcus PCN/AMP Gent 6wks Vanco
Gent 6wks Staph infection Cefazolin 6wks /-
Gent 5days Vanco 6wks HACEK Organisms Ceftriaxo
ne 4wks
43
Prosthetic valve Streptococcus-PCN
sensistive Ceftriaxone 6wks Gent 2wks
Vanco 6wks Streptococcus-PCN resistant
Strep Vanco 6wks Enterococci PCN or Amp 6wks
Gent 6wks VancoGent 6wks Methicllin
Susceptible Staph Nafcillin 6wks Gent 2wks
Rifampin 6wks MRSA Vanco 8wks Gent 2wks
rifampin 8wks HACEK Ceftriaxone
6wks Diptheroides PCN Gent 6wks Vanco 6wks
44
Surgical Intervention
The outcome of surgery is better when the
infection is partially treated or healed. So,
patients with severe valve dysfunction who
respond to antibiotic therapy and who manifest
evidence of only mild and nonprogressive heart
failure should complete a full course of
antibiotics before surgery is undertaken to
minimize morbidity and mortality. However,
surgery should not be delayed to complete
antimicrobial therapy in patients with
progressive heart failure or evidence of other
complications. Two general classes of valves
exist, bioprosthetic and mechanical.
45
Prosthetic Valves
46
Class I indication for native valve
surgery Acute AR or MR with heart failure Acute
AR with tachycardia or early closure or MV on
echo Fungal endocarditis Aortic or annular
abscess, or aortic aneurysm Valve dysfunction or
infection after 10 days of Abx therapy Class II
indication for native valve surgery Recurrent
emboli after 24hrs Abx therapy Mobile
vegetations 10mm
47
Recommendation for Bioprosthesis placement Pt
cannot take warfarin 65yrs who do not need
warfarin for another cause Recommendation for
mechanical valve placement Expected long life
span Mechanical valve in another position Pt with
renal failure or hypercalcemia Require warfarin
for another cause
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49
Non-bacterial Thrombotic Endocarditis
Combination of endothelial injury and
hypercoagulable state can lead to
platelet-thrombin deposition. These deposits
are found on the atrial side of MV TV, and the
ventricular side of AV PV similar to location
of infective vegetations. Most common associated
syndrome with this condition is the
anti-phospholipid syndrome. The atypical
verroucous Libman-Sacks vegetations are usually
difficult to see on TTE. They usually accumulate
on the distal tip of the MV.
50
Metastatic tumours can also involve cardiac
valves and produce lesions similar to IE. These
marantic endocarditis lesions occur more
frequently in Hodgkin and adenocarcinoma of the
lung, stomach and colon. All non bacterial
thrombotic lesion can become infected if exposed
to bacteremia.
51
Antibiotic Prophylaxis
Bacteria colonize and adhere to platelet-fibrin
aggregates during bacteremia. Although many
bacteria enter the blood stream, only those
suited to adhere to surfaces can become
infective. Certain predisposing valvular
lesions are also required to increase your risk
of colonization. This has led to identifying
patients at risk during surgical procedures and
the use of prophylactic antibiotics.
52
Prophylaxis recommended Dental procedures,
including scaling and cleaning Tonsillectomy
adenoidectomy Surgery involving GI or upper
respiratory mucosa Esophageal varices
sclerotherapy ERCP Cholecystectomy Cystoscopy,
urethral dilatation GU surgery Incision and
drainage of infected tissue
53
Prophylaxis not recommended Dental procedures
not likely to produce bleeding, i.e. filling
above gum line, orthodontic adjustments. Endotrach
eal intubation TEE Flexible bronchoscope /-
biopsy Angiography /- PTCA Pacemaker
implantation GI Endoscopy /- biopsy C-section In
absence of infection uncomplicated vaginal
delivery, therapeutic abortion, IUD, laparoscopy,
circumcision.
54
High Risk Patients Prosthetic valve Prior
IE Cyanotic congenital heart disease PDA AR AS MR
MS MR VSD Coarctation of Ao Surgically
constructed systemic-pulmonary shunts Surgically
corrected cardiac lesion with residual
hemodynamic abn or prosthesis.
55
Intermediate Risk Patients MV prolapse or
thickening with murmur Pure MS TV
disease PS Asymmetrical septal hypertrophy Bicuspi
d AV with minimal hemodynamic changes Ao
sclerosis with minimal hemodynamic
changes Surgically repaired intracardiac lesions,
less than six mos postop, with minimal
hemodynamic changes.
56
Low Risk Patients MV prolapse without
murmur Isolated secundum ASD Implanted
devices CABG Prior Kawasakis or Rheumatic
disease without valvular dysfunction
57
Antibiotic Prophylaxis Summary
GI/GU regimen High risk Amp 2g Gent 1.5mg/kg.
Mod risk Amox 2g or Amp. PCN allergy
Substitute Vanco 1g Oral/Esoph/Resp
regimen Amox PO or Amp IV PCN allergy
Substitute Clinda 600mg PO/IV
Cefazolin 1g
Azith/Clarith PO
500mg Abx should be given prior to procedure,
1hr for oral
1/2hr
for parenteral
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Questions?
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UTD Abx Tables
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UTD Surgery tables
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