Infect Dis Clin N Am 16 (2002) 453475

Current best practices and guidelines

Indications for surgical intervention
in infective endocarditis
Lars Olaison, MD, PhDa,*, Gosta Pettersson, MD, PhDb
a

Department of Infectious Diseases, Sahlgrenska University Hospital,

S-416 85 Goteborg, Sweden
b
The Cleveland Clinic Foundation, Thoracic and Cardiovascular Surgery/F25,
9500 Euclic Avenue, Cleveland, OH 44195, USA

The role of surgery in active infective endocarditis (IE) has been expanding since the rst report of successful ventricular septal repair and removal
of tricuspid vegetation in 1961 and the rst successful valve replacement
during active IE in 1965 [1,2]. The reduction of mortality in IE during the
last three decades from 25% to 30% to 10% to 20% may be due chiey to
more aggressive surgical intervention in cases with congestive heart failure
(CHF), complicated invasive infections with abscesses and aneurysms, and
prosthetic valve infections. For IE caused by Staphylococcus aureus in particular, a reduction of mortality from 50% to 60% to 15% to 30% has been
achieved.
The results of surgery depend upon many factors. The general preoperative condition of the patient, antibiotic treatment, timing of surgery, perioperative management, surgical techniques (including choice of methods
for reconstruction), postoperative management, and follow-up are all
important determinants of outcome. Considerations of the indications for
surgery, the timing, and evaluation of the patients ability to withstand the
contemplated operation are all highly dependent upon the experience of
both the surgeons and their institutions. These are complicated decisions,
requiring sound judgment based upon extensive clinical experience. New
problems have emerged that are associated with an increasing number of
patients in intensive care units (ICUs) and other hospital settingsincluding

This work was supported by grants from the Swedish Heart and Lung Foundation and the
National Board of Health and Welfare, Sweden.
* Corresponding author.
E-mail address: lars.olaison@medfak.gu.se (L. Olaison).
0891-5520/02/$ - see front matter
2002, Elsevier Science (USA). All rights reserved.
PII: S 0 8 9 1 - 5 5 2 0 ( 0 1 ) 0 0 0 0 6 - X

454

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

chronic hemodialysiswho develop nosocomial endocarditis. This group of

patients has high mortality and is often considered inoperable [3,4], but
some can be salvaged by judicious surgical intervention.
Published experience of surgical treatment during active endocarditis
from the 1990s reported mortality rates of 8% to 16%, with actuarial
survival at 5 years of 75% to 76% and at 10 years of 61% [510]. Preoperative New York Heart Association (NYHA) classication, age, and
preoperative renal failure are common predictors of operative mortality
in logistic regression analyses. Aggressive disease of shorter duration, most
often being acute endocarditis caused by S. aureus, is associated with higher
mortality.
A series of illustrations have been included to illustrate some of our general concepts (Figs. 17). The gures illustrate some typical pathologies as
well as surgical principles and options.

Fig. 1. Operative specimen from a fatal case of S. aureus aortic valve endocarditis aecting a
valve with preexisting calcic aortic valve stenosis. The vegetations and the invasive lesion are in
the typical location underneath a commissure, in this case between the right and noncoronary
cusps. There is destruction and perforation of the right cusp through to the pericardium,
resulting in the fatal tamponade. The conduction bundle is located under the central brous
body (CFB) and is not destroyed.

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

455

Fig. 2. Aortic valve endocarditis caused by S. aureus not responding to antibiotic treatment.
Surgery disclosed extensive periaortic cellulitis with infection and necrosis (white arrows)
involving the space between the aortic root and the wall of the right atrium (RA), spreading
anteriorly in the epicardial fat.

Timing of surgery
The duration of antibiotic therapy before the operation appears to have
no inuence on operative mortality [911]. It is, however, considered important to have adequate antibiotic coverage during operation to kill bacteria
entering the circulation during the surgical debridement. In a Swedish 5-year
national study 223 patients underwent cardiac surgery during treatment, one
third during the rst 5 days and 52% during the rst 10 days of treatment.
Treatment mortality was equal (8.5%) for patients subjected to surgery within the rst 10 days and after 10 days (data from the National Swedish Endocarditis Registry).
Some authors have found operation during the acute phase of endocarditis to be associated with a higher risk of persistent or early recurrent
prosthetic valve endocarditis (PVE) [12,13]. Others did not nd an increased
recurrence rate [14], particularly not after surgery for mitral valve endocarditis [13,1518]. In addition to the postoperative antibiotic treatment, radical debridement and the method of reconstruction utilized are important
determinants of the risk for persistent and recurrent infection, as illustrated
by the improving early and late results over the last decade.

456

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

Indications for surgery

The indications for surgery are dened more precisely today than in the
past [13,14] due to increased experience and the renement of echocardiography, particularly the introduction of transesophageal imaging.
Surgery is necessary in approximately 25% to 30% of cases during the
acute phase of infection, and in another 20% to 40% in later or secondary
phases [1921]. In general, the prognosis is better after early surgery undertaken before the cardiac pathology and the general condition of the patient
have deteriorated too severely [2023]. The nal outcome has little relation

Fig. 3. Prosthetic aortic valve endocarditis. Complete heart block developed two days
preoperatively. (A) shows the right atrial (RA) view of the infection invading the triangle of
Koch with destruction of the atrioventricular (AV) node (white arrows) anterior to the coronary
sinus (CS). (B) displays the full extent of the circumferential horseshoe abscess after
debridement. The process originally started anteriorly, underneath the right coronary artery
(RCA) where the cavity was communicating with the circulation, irrigated by blood and
eventually endothelialized. To the left and posterior the infection is still active and destructive,
eventually penetrating into the oor of the right atrium and the triangle of Koch to cause
destruction of the AV node and complete heart block. The left ventricular outow tract is well
preserved with stay sutures placed in the two trigones on either side of the base of the anterior
mitral leaet (MV). (C) demonstrates the reconstruction of the heart with an autologous
pericardial patch to reconstruct the free wall of the right atrium and an aortic homograft to
reconstruct the left ventricular outow tract. Monolament polypropylene sutures are used.
LVOT left ventricular outow tract; TV tricuspid valve.

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

Fig. 3 (continued )

457

458

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

to the duration and intensity of antibiotic therapy prior to surgery [5,24,25].

This observation is important to remember with regard to the decision to
perform early surgery.
The decision to undertake surgery should be based on careful daily clinical evaluations, microbiological tests (including follow-up blood cultures
during antibiotic treatment), and the information provided by repeated
echocardiographic examinations.
Indications for surgery, ranked with respect to degree of urgency, are
presented in Table 1. These can be divided into the following categories,
according to the phase of the disease and the objectives of the operation.
Congestive heart failure
Moderate and severe (NYHA class III or IV) or progressive heart failure
due to valvular dysfunction are the most common and best validated indica-

Fig. 4. (A) and (B): Even in the presence of advanced pathology, including annular destruction
and development of periaortic cavities, the left ventricular outow tract is most often well
preserved. (A) and (B) show two cases in which the Ross operation (pulmonary autograft
reconstruction of the left ventricular outow tract and homograft replacement of the
pulmonary valve) has been used for aortic valve endocarditis. The removal of the pulmonary
artery (the autograft) provides unparalleled exposure of the left ventricular outow tract and
the pathology. The autograft allows insertion of living tissue into the infected area with minimal
use of foreign material.

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

459

Fig. 4 (continued )

tions for surgery in patients with IE, being the main indication in 22% to
71% in dierent series [8,15]. Acute onset of aortic insuciency is tolerated
poorly, and heart failure secondary to aortic regurgitation is generally considered to be severe and likely to progress rapidly. Congestive heart failure
(CHF) may also develop acutely from rupture of infected mitral chordae,
perforation of native or bioprosthetic valve leaets and cusps, valve obstruction, or sudden development of intracardiac shunts from stulous tracts or
prosthetic valve dehiscence.
A progressive worsening of valvular regurgitation and ventricular dysfunction may also lead to more gradual onset of CHF despite appropriate
antibiotic therapy. Mild CHF at the time of initial diagnosis may progress
to severe CHF during treatment, usually within the rst month of therapy.
CHF in IE carries a worse prognosis with medical therapy alone, but also
constitutes a surgical risk factor. Delaying cardiac surgery, thus allowing
more severe cardiac decompensation to develop, dramatically increases
operative mortality: from 6% to 11% for patients without CHF to 17% to
33% for patients with CHF [26]. In addition, delay exposes the patient to the
risk of perivalvular extension of the infection with increased likelihood of
serious secondary complications.
Four studies from the 1970s and 1980s have compared medical and combined medical and surgical treatment of CHF in IE. All showed a reduction

460

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

of mortality with surgery, from 56% to 86% to 11% to 35%, although no

correction was made for interfering underlying conditions [2730]. In two
Swedish studies mortality rates for surgically treated versus non-surgically
treated decompensated patients were 9% versus 20% and 10% versus 27%
(P < 0.05), respectively. The greatest benet of early surgery was noted in
patients with new heart failure at entry who underwent surgery on median
treatment day 4 [9,31]. The infected valve plays an important role. Aortic
regurgitation with tachycardia and early closure of the mitral valve as a sign
of uncompensated ventricular overload is an urgent indication for surgery as
well as acute aortic or mitral regurgitation with progressive heart failure.
Aortic insuciency due to pre-existing valve disease may be treated conservatively if the patient remains compensated, but new-onset, moderate, or
severe aortic regurgitation due to IE usually requires surgery. Mitral regurgitation is usually better tolerated and has a better prognosis because the left
atrium and the pulmonary vascular bed can better accommodate the regurgitant volume than the left ventricle alone, as occurs in aortic regurgitation.

Fig. 5. (A) and (B): Double (aortic and mitral) valve endocarditis with typical location of
secondary kissing/jet lesion on the anterior mitral leaet seen from the aortic side. The
indication for surgery was congestive heart failure due to severe regurgitation through both
valves. (B): Mitral lesions of this size and location are repaired with a patch of autologous
pericardium.

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

461

Fig. 5 (continued )

Cardiac decompensation may occur when the chordae tendinae rupture, but
the left ventricle often adapts to the overload.
Right-sided IE requires surgery less often because tricuspid or pulmonic
regurgitation is well tolerated as long as the pulmonary vascular resistance is
not signicantly elevated.
The risk of development of acute heart failure is also related to virulent
pathogens, such as S. aureus, hemolytic streptococci group AC, F, and G,
or Streptococcus pneumoniae, but any microorganism may cause this complication if treatment is delayed long enough.
Periannular extension of infection
Peri-annular and para-annular abscesses can be dicult to diagnose with
certainty, even with transesophageal echocardiogram (TEE). The sensitivity
for the diagnosis of abscesses in a French multicenter study of perivalvular
abscesses was 36% and 80%, respectively, using transthoracic echocardiography (TTE) and TEE [32]. In other studies of TEE the sensitivity was
76% to 100% for dening periannular extension of IE while retaining a specicity of 95% [3335]. Extension beyond the leaets is common, occuring
in 10% to 40% of all episodes of native valve endocarditis (NVE). This
complication occurs more commonly with aortic IE than with mitral or

462

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

Fig. 6. The patient presented with stroke and cerebral infarct. Vegetation and perforation in the
medial scallop of the posterior mitral leaet causing 34+ mitral regurgitation. Surgery was
postponed for one week. The valve pathology was debrided and the valve repaired with the use
of an autologous pericardial patch.

tricuspid infection. In PVE it is even more common, occurring in 56% to

100% of all patients.
Extension of infection to deep tissue begins as cellulitis and eventually
progresses to abscess formation. Hemodynamic pressure eects on perivalvular tissue weakened or destroyed by infection will result in formation of
pseudoaneurysms. Drained abscesses are converted to pseudoaneurysms
or blood-lled cavities when the pus and necrotic material are washed away
by the ow of blood. The same infectious process can be in dierent stages
of activity, working its way around the circumference of the valve in a horseshoe fashion [36]. Destruction of the aortic or mitral annulus will result in
partial or circumferential ventriculo-aortic or atrio-ventricular separation,
respectively. If an abscess breaks through to another heart chamber, a stula
is formed. A rupture through to the pericardium is a catastrophe, usually
fatal. In aortic valve endocarditis, the peri-valvular invasion often begins
under the commissures. From there, annular destruction spreads around the
root on top of the interventricular septum and underneath the pulmonary artery into areas previously occupied by periaortal and epicardial

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

463

fat. Proximal tissue loss caused by invasion and necrosis of ventricular

musculature is less common, but when it occurs surgical reconstruction presents a more dicult problem. If the infectious process enters into the triangle
of Koch, inammation or destruction of the atrioventricular node and
bundle of His often results in heart block.
Aortic valve involvement and intravenous drug abuse are the only known
independent risk factors for perivalvular abscesses [37]. Development of new
AV-block on ECG during the course of endocarditis carries an 77% positive
predictive value for abscess formation, but has a relatively low sensitivity of
42% [38]. Acute surgery is benecial in most of these patients because delay
may compromise cardiac function with a resultant higher perioperative risk
[39, 40]. In a recent series of 25 patients with aortic valve abscesses 20 (80%)
underwent surgical intervention. Mortality for surgically treated patients
was 30% as compared to 100% for patients without surgery. S aureus was
isolated in 73% of the fatal cases [41]. The presence of annular abscesses
was not an adverse predictor of early mortality in a series presented by
Bauernschmitt et al.; provided the surgical procedures were radical, the
abscess cavities were completely resected and approximately normal hemodynamics could be restored [6]. Early reinfection rate was low (2%) despite
insertion of mechanical valves. For patients with large abscesses at the aortic
root, however, a radical resection carries the risk of destruction of the conduction system with resultant postoperative AV-block.
A small number of patients may be treated successfully without surgical
intervention, especially those who do not have heart block, echocardiographic evidence of progression during therapy, valvular dehiscence, or
insuciency. These patients should be monitored closely with serial TEE
and followed at least 2 months after completion of antimicrobial therapy
with repeated TEE [26,42,43]. The signicance of residual cavities after
microbiologic cure of endocarditis for long-term prognosis and risk of
recurrent endocarditis remains unresolved. A larger-sized cavity, recent
endocarditis, signicant valvular regurgitation, and younger age are factors
that favor corrective surgery in such cases.
Vegetations and risk of systemic embolization
A vegetation can be visualised by echocardiography in 13% to 78% of IE
episodes; this is not per se an indication for surgery [44]. Clinically signicant embolic events are common, with a cumulative incidence (including
pretreatment and post-treatment) ranging from 10% to 50% [4447]. In the
pre-antibiotic era, cerebral embolism was one of the major causes of death,
being second only to progressive heart failure. In modern times, emboli are
directly responsible for about 25% of fatalities and for a substantial proportion of irreversible sequelae after microbiological cure. Three quarters of
clinically diagnosed emboli occur before antibiotic treatment begins; thus
only one quarter of all emboli are potentially preventable [48].

464

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

Fig. 7. (A) and (B): Composite graft endocarditis with mediastinal abscess surrounding the
graft, perivalvular leak and valve thrombosis. (B) illustrates the circumferential pathology. Note
successfully that the left ventricular outow tract is well preserved. The patient was re-operated
with complete debridement of the infected necrotic tissue as well as all foreign material and
reconstructed with an aortic homograft.

Up to 50% to 65% of embolic events involve the central nervous system,

the majority involving the distribution of the middle cerebral artery. When
considering that the brain receives approximately 14% of the cardiac output,
but accounts for about 50% of clinical embolic events, it is apparent that
many emboli to other sites must remain undiagnosed.
The risk for clinically apparent emboli during treatment was 14% and
21%, respectively, among patients with denite vegetations or larger-sized
(10 mm) vegetations at the start of therapy in two series from the Mayo
Clinic and Goteborg, Sweden, while absence of vegetations indicated a risk
of 11% and 8% in the same series [31,44]. The series were performed to a
large extent with utilization of the less sensitive TTE technique. These are
the only studies that report the changing incidence of embolism over time
during antibiotic treatment. They show that the frequency of embolism
decreases after only one week of treatment (Fig. 8).
Attempts have been made to grade dierent risk factors to predict the risk
of embolization for an individual patient. In the Mayo study mentioned
above, the strongest risk factor (irrespective of vegetation size) was atrial
brillation, followed in rank order by S. aureus etiology, history of previous

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

465

Fig. 7 (continued )

embolism, short symptom duration, mitral valve location, and older age. In
the Swedish study, the rank order of risk factors was PVE (which was not
studied in the Mayo Clinic patients), followed by S. aureus etiology, older
age, short symptom duration, mitral valve location, and a history of previous embolism.
Many studies have tried to use the echocardiographic charcteristics of the
vegetations and other pathological ndings to identify a sub-group of
patients who might benet from early surgery to prevent embolism. Conicting results of correlation between vegetation size and embolization have
been seen in studies using TEE. In one study mitral vegetations 10 mm in
diameter were associated with the highest rate of embolism (25%). The
highest embolic rate (37%) was seen in the subset of patients with mitral
vegetations attached to the anterior rather than the posterior leaet. The
mechanical stress of broad and abrupt leaet excursions may give rise to
fragmentation and embolization of the vegetation [49]. Vegetation size
>20 mm predicted embolic events in another TEE study [50]. Two other
studies, however, failed to demonstrate this relationship, possibly due to
relatively small numbers of patients [45,47]. A recent study using TEE combined with careful clinical examinations and investigations to detect silent
emboli found a signicantly higher incidence of embolism associated
with vegetations 10 mm (60%), mobile vegetations (62%), and in particular

466

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

Table 1
Indications for surgery in patients with infective endocarditis
Indication

Evidence based

Emergency indication for cardiac surgery (same day)

1. Acute AR with early closure of mitral valve
2. Rupture of a sinus Valsalva aneurysm into the right heart chamber
3. Rupture into the pericardium

A
A
A

Urgent indication for cardiac surgery (within 12 d)

4. Valvular obstruction
5. Unstable prosthesis
6. Acute AR or MR with heart failure, NYHA IIIIV
7. Septal perforation
8. Evidence of annular or aortic abscess, sinus or aortic true or false
aneurysm, stula formation, or new onset conduction disturbances
9. Major embolism + mobile vegetation >10 mm + appropriate antibiotic
therapy <710 d
10. Mobile vegetation >15 mm + appropriate antibiotic therapy <710 d
11. No eective antimicrobial therapy available
Elective indication for cardiac surgery (earlier is usually better)
12. Staphylococcal prosthetic valve endocarditis
13. Early prosthetic valve endocarditis (2 mo after surgery)
14. Evidence of progressive paravalvular prosthetic leak
15. Evidence of valve dysfunction and persistent infection after 710 d of
appropriate antibiotic therapy, as indicated by presence of fever or
bacteremia, provided there are no noncardiac causes for infection
16. Fungal endocarditis caused by a mold
17. Fungal endocarditis caused by a yeast
18. Infection with dicult-to-treat organisms
19. Vegetation growing larger during antibiotic therapy >7 d

A
A
A
A
A
B
C
A
B
B
A
A

A
B
B
C

A Strong evidence or general agreement that cardiac surgery is useful and eective;
B Inconclusive or conicting evidence or a divergence of opinion about the usefulness/ecacy
of cardiac surgery, but weight of evidence/opinion of the majority is in favor; C Inconclusive
or conicting evidence or a divergence of opinion; lack of clear consensus on the basis of
evidence/opinion of the majority. AR aortic regurgitation; MR mitral regurgitation;
NYHA New York Heart Association classication.

with the combination of severely mobile and large vegetations (15 mm)
(83%) [46]. S. aureus infection was a risk factor, while mitral localization had
no association to risk of embolic event.
In one study, large vegetations independently predicted embolic events
only in the viridans streptococci group, while staphylococcal infections carried a high risk of embolization that was independent of vegetation size [44].
When should preventive removal of vegetations by means of surgery be
recommended? Traditional indications for surgery to avoid embolization
in IE patients have been two or more major embolic events during therapy.
Every patient should be considered in light of the specic risk factors for
embolization mentioned above. The duration of antibiotic treatment should
also strongly inuence the decision because the risk of embolism decreases
rapidly after the rst week of eective treatment.

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

467

Fig. 8. Incidence of embolic events per 1000 treatment days during treatment of infective endocarditis in Goteborg [30] and the Mayo Clinic [41]. (From Alestig K, Hogevik H, Olaison L.
Infective endocarditis: a diagnostic and therapeutic challenge for the new millenium. Scand
J Infect Dis 2000;32:34356. Copyright 2000 Taylor & Francis [31]).

Urgent surgery is recommended during the rst 10 to 14 days of treatment

in cases of recurrent embolism after a second embolic complication. Surgery
should also be considered seriously after an initial embolic episode when
echocardiography shows a remaining large, mobile vegetation. Vegetations
localized on the anterior mitral leaet might carry a higher risk of embolism,
even if the last published series failed to show any correlation [46].
Should surgery be recommended when echocardiography reveals large,
mobile vegetations but embolization has not yet occurred? If the patient has
signicant heart failure or severe valvular dysfunction, the decision is clear
because surgery will achieve a two-fold objective. However, when valvular dysfunction is modest, the surgical indication is unclear. In general, the authors
do not recommend surgery solely to prevent embolization. If a large, mobile
vegetation is located on the mitral valve, the decision to operate is somewhat
favored because in this situation it is often possible to perform conservative
debridement of the vegetation and valve repair without valve replacement.
Persistent bacteremia
Persistent bacteremia in the absence of an extracardiac source of bacteremia indicates a failure of antibiotic therapy, provided treatment is given

468

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

according to accepted recommendations. The time considered necessary to

identify such a failure is considered to be at least 7 days after initiation of
antibiotic therapy. Provided that all eorts have been made to exclude metastatic foci, the most plausible cause is intracardiac suppurative disease, which
requires surgical intervention. Fever during treatment should not automatically be regarded as synonymous with persistent bacteremia or suppurative
disease; it must be analyzed in terms of persistent and recurrent fever. Fever
persisted more than one week or recurred, despite eective antibiotic treatment, in 57% of 193 episodes in a study of IE treatment. Persistent fever was
caused by a complicating cardiac infection in 56% of the episodes. On the
other hand, recurrent fever, which occurred most commonly during the third
and fourth weeks of treatment, was caused by hypersensitivity reactions to
b-lactam antibiotics in the majority of episodes [51,52].
Valve obstruction
Mechanical obstruction of prosthetic valves or the native mitral valve by
large vegetations or thrombi is an urgent indication for surgery, particularly
if the valve is a mechanical valve prosthesis.
Fungal endocarditis
The earliest reported intracardiac surgical intervention for active IE was
in 1961 in a patient with Candida albicans endocarditis [1]. Candida and
Aspergillus species cause the majority of fungal IE cases. Amphotericin B,
still the only fungicidal agent available, has poor penetration into vegetations and surgery is usually needed. Most cases of fungal IE are complicated
with bulky vegetations, metastatic infections, perivalvular infections, or
embolization to large blood vessels [53,54]. Virtually all complicated cases
need surgery. In uncomplicated episodes caused by Candida species, a number of case reports of NVE and PVE patients who are not valve replacement
candidates suggests that medical therapy alone may be successful, although
long-term suppressive therapy of at least 2 years with imidazoles is usually
employed [53,54]. Aspergillus endocarditis carries a mortality risk of 90% to
100% without surgery.
Unstable prosthesis
The development of a rocking prosthesis or a rapidly progressive paravalvular leak are urgent indications for valvular surgeryespecially during
the early postoperative periodin a patient with early PVE.
Dicult-to-treat organisms
Pseudomonas aeruginosa is a rare agent of IE, and is in most cases connected with intravenous drug abuse. Isolated right-sided pseudomonal IE

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

469

can generally be managed successfully with antibiotics with or without surgery. Medical therapy alone has rarely been eective in left-sided IE; valve
replacement is indicated for the optimal chance of achieving cure [55].
Coxiella burnetti, which causes Q-fever, is a strict intracellular pathogen.
Patients with previously damaged aortic or mitral valves or prosthetic valves
might acquire IE. Eradication of the organism with medical therapy alone is
unlikely, and reinfection of prosthetic material after surgical replacement
is common. Valve replacement is recommended only for CHF, PVE, or
uncontrolled infection [56]. To prevent reinfection of prosthetic material
some experts recommend that antimicrobial therapy be continued longterm, possibly indenitely [57].
Brucellae are intracellular gram-negative bacilli that can cause IE complicated by development of valve destruction, perivalvular abscesses, and
CHF. Few patients have been cured with antimicrobial therapy alone; most
require valve replacement for cure [58].
Staphylococcus lugdunensis is a coagulase-negative staphylococci that
often causes a destructive course of infection with a frequent need for valve
replacement.
No eective antimicrobial agent available
In the rare case that no eective antimicrobial agent is available, IE
usually is caused by fungi or vancomycin-resistant enterococci. In such cases
surgery provides the only means capable of eradicating the infection.
Prosthetic valve endocarditis
Perivalvular invasive infections are common in PVE, especially when the
infection arises within 12 months after surgery or involves an aortic prosthesis [59]. The microbial etiology of early PVE is dominated by coagulasenegative staphylococci and S. aureus, accounting for about 30% and 20%
of the cases, respectively [12]. In nearly all these patients, infection spreads
behind the site of attachment of the valve prosthesis, resulting in valve ring
abscesses and valve dehiscence in 60% of cases. If murmurs suggestive of
valve dysfunction, moderate to severe CHF, persistent fever 10 days, or
new ECG conduction abnormalities appear as signs of an invasive infection,
surgical treatment results in higher survival rates, less relapses, less rehospitalization for valve surgery, and less delayed mortality due to IE than medical treatment alone [5962]. The rate of recrudescent PVE after surgery is
reported to be 6% to15%, and repeat surgery is required for recurrent PVE
or prosthesis dysfunction in the new prosthesis in 18% to 26% of patients
[59,6365]. These gures indicate that these operations are very demanding
technically. Radical debridement and reconstruction are often needed,
requiring highly experienced surgeons. Multiple studies have shown that
PVE caused by S. aureus is most eectively treated with early surgery and
antibiotics [13,62].

470

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

There are a few subsets of patients in whom medical therapy alone may
be eective for PVE. These patients usually have late-onset of infection (12
months after prosthesis insertion), infection by viridans streptococci,
HACEK (Haemophilus spp, Actinobacillus acinetocomitans, Cardiobacterium
hominis, Eikenella spp, Kingella kingae) or enterococci and absence of evidence of invasive infection. Early antibiotic treatment improves the
chances of cure without complications in these patients with late-onset PVE
[42,66].

Additional issues related to surgical decision making in the acute phase

Neurological complications
Evaluation and management of patients with neurologic symptoms
represents another dicult and controversial area. The incidence of neurologic complications diers in the literature from 15% to 40% [11,46,48]. Neurologic complications include transient ischemic attack (TIA), embolic
stroke with or without hemorrhage, ruptured mycotic aneurysms, meningitis, and non-focal encephalopathy.
The cardiac surgeon has two concerns: the rst is related to the immediate risk of intracranial bleeding during cardiopulmonary bypass [67], and
the second is related to the risk associated with short- and long-term anticoagulation.
Benets versus risks should be carefully analyzed [68]. TIA or embolic
stroke without hemorrhage is the most common complication, constituting
62% of pathologically proven episodes in one study [48]. Hemorrhage from
rupture of a mycotic aneurysm or septic arteritis artery occurs less often but
entails a higher operative risk and a higher risk associated with anticoagulation. Since the majority of patients with infective endocarditis and cerebral
symptoms have neither bleeding nor mycotic aneurysms, it is not possible to
give rm recommendations about the necessary preoperative evaluation.
There is a consensus regarding the recommendation that a preoperative
CT scan of the brain be performed on every patient with neurologic symptoms to clarify the nature and extent of any cerebral lesion and to identify
hemorrhagic infarcts and other bleeding. In patients with intracranial bleeding identied on CT scan 10% to 50% will have a ruptured mycotic aneurysm [69,70]. Cerebral angiography is recommended in these patients. A
ruptured mycotic aneurysm should be resected, clipped, or embolized before
cardiac operation [69].
Ting et al. [71] have shown that operative mortality increased in the preoperative presence of a hemorrhagic infarct but not in the presence of an
ischemic infarct. In the absence of a hemorrhagic infarction, valve replacement can be performed at least 72 hours after the accident, with a low risk of
perioperative stroke [67]. However, a recent multicenter retrospective study
in Japan showed that there remains an increased risk of exacerbation of the

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

471

neurological decits for weeks, but that this risk lessens with time irrespective of the type of lesion [68].
Patients with a recent hemorrhagic infarction clearly have an increased
risk of intracranial bleeding during surgery [71]. The current recommendation is to allow an interval of 2 to 3 weeks between the neurologic event and
cardiac operation based on small published series [69,72].
Parrino et al. found diuse encephalopathy to be associated with poor
outcome, focal decit associated with 21% mortality, and 18% risk of deterioration of the neurological decit. The question remains, however, if
delaying surgery does anything other than select out hardier patients [73].
As a basic rule, operations should be delayed in unconcious patients and
patients unable to follow simple commands until neurological improvement
has been demonstrated.
Extracardiac invasive infections
Extra-cardiac lesions are not always explained by emboli. Some are due
to mycotic aneurysms, infectious arteritis, and other septicemic processes. In
the case of diagnosis of a visceral abscess (most often splenic), this should be
treated before cardiac surgery [74].
Extra-cardiac manifestations (most often in the form of stroke) often
precede the cardiac manifestations of IE. A high index of suspicion for
the diagnosis of IE is important in such circumstances, to prevent missing the
opportunity of early detection.
Age
Increased age is another risk factor. The population is becoming older;
the fact that a 9-fold increased rate of endocarditis has been reported for
patients older than 65 years is important [44,75]. Age per se is not a contraindication for surgery. Coronary angiography before surgery can be useful
in elderly patients, in patients with previous coronary grafting, and in
patients with advanced pathology and abscesses that may necessitate complex repairs. The increased risk of emboli during catheter manipulation in
the aortic root should be considered.
Drug abuse
Intravenous drug abuse (IVDA) is associated, among other complications, with increased risk of blood-borne viral disease, non-compliance with
medical regimens, and recurrent endocarditis. The predominance of isolated
right-sided involvement in IE in this group with lower hemodynamic pressures implies a less aggressive infection with excellent short-term prognosis
despite the frequent isolation of S. aureus in blood cultures. Heart surgery is
seldom indicated. The frequency of left-sided involvement in IVDA has,
however, been relatively high33% and 39%in two series from Denmark

472

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

and Sweden, respectively [76] (data from the National Swedish Endocarditis
Registry). In the Swedish 5-year study involving 138 cases of IE in IVDA,
left-sided involvement as compared to isolated right-sided involvement
necessitated heart surgery in 35% versus 6% of the episodes. Mortality rates
for the two groups were 21% and 0%, respectively. The indications for surgical
intervention in patients with IVDA with left-sided endocarditis are the same as
for non-users, while the indications for surgical intervention in isolated tricuspid endocarditis are very limited. Furthermore, the hazards of overdosing and
underdosing anticoagulant therapy in this group of patients must be kept in
mind when surgery and surgical technique is considered. In an article by Mathew et al., the overall 5-year survival rate was 70% for 80 surgically treated
patients with IVDA, while 5-year event-free survival was only 52%; the events
were recurrent endocarditis, stroke, bleeding, and systemic embolism [77].

References
[1] Kay JH, Bernstein S, Feinstein D, et al. Surgical cure of Candida albicans endocarditis with
open-heart surgery. New Engl J Med 1961;264:90710.
[2] Wallace AG, Young WG, Osterhout S. Treatment of acute bacterial endocarditis by valve
excision and replacement. Circulation 1965;31:4503.
[3] Gouello JP, Asfar P, Brenet O, et al. Nosocomial endocarditis in the intensive care unit: an
analysis of 22 cases. Crit Care Med 2000;28(2):37782.
[4] McCarthy JT, Steckelberg JM. Infective endocarditis in patients receiving long-term
hemodialysis. Mayo Clin Proc 2000;75(10):100814.
[5] Alexiou C, Langley SM, Staord H, et al. Surgery for active culture-positive endocarditis:
determinants of early and late outcome. Ann Thorac Surg 2000;69:144854.
[6] Bauernschmitt R, Jakob HG, Vahl C-F, et al. Operation for infective endocarditis: results
after implantation of mechanical valve. Ann Thorac Surg 1998;65:35964.
[7] Haydock D, Barratt Boyes B, Macedo T, et al. Aortic valve replacement for active
infectious endocarditis in 108 patients. A comparison of freehand allograft valves with
mechanical prostheses and bioprostheses. J Thorac Cardiovasc Surg 1992;103:1309.
[8] McGin DC, Galbraith AJ, McLachlan GJ, et al. Aortic valve infection. Risk factors for
death and recurrent endocarditis after aortic valve replacement. J Thorac Cardiovasc Surg
1992;104:51120.
[9] Olaison L, Hogevik H, Myken P, et al. Early surgery in infective endocarditis. Q J Med
1996;89:267378.
[10] dUdekem Y, David TE, Feindel CM, et al. Long-term results of surgery for active
endocarditis. Eur J Cardiothorac Surg 1997;11:4652.
[11] Agnihotri AK, McGin DC, Galbraith AJ, et al. The prevalence of infective endocarditis
after aortic valve replacement. J Thorac Cardiovasc Surg 1995;110:170820.
[12] Chastre J, Trouillet JL. Early infective endocarditis on prosthetic valves. Eur Heart J
1995;16(Suppl B):328.
[13] Wol M, Witchitz S, Chastang C, et al. Prosthetic valve endocarditis in the ICU.
Prognostic factors of overall survival in a series of 122 cases and consequences for
treatment decision. Chest 1995;108:68894.
[14] Verheul H, Renee B, Vanden Brink A, et al. Eects of changes in management of active
infective endocarditis on outcome in a 25-year period. Am J Cardiol 1993;72:6827.
[15] Aranki S, Santini F, Adams D, et al. Aortic valve endocarditis. Determinants of early
survival and late morbidity. Circulation 1994;90(SII):17582.

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

473

[16] Edwards MB, Ratnatunga CP, Dore CJ, et al. Thirty-day mortality and long-term survival
following surgery for prosthetic endocarditis: a study from the UK heart valve registry. Eur
J Cardiothorac Surg 1998;14:5664.
[17] Horstkotte D, Piper C, Wiemer M, et al. Emergency heart valve replacement after acute
cerebral embolism during orid endocarditis. Med Klin 1998;93:28493.
[18] Aranki SF, Adams DH, Rizzo RJ, et al. Determinants of early mortality and late survival
in mitral valve endocarditis. Circulation 1995;92(SII):1439.
[19] Delahaye F, Ecochard R, de Gevigney G, et al. The long term prognosis of infective
endocarditis. Eur Heart J 1995;16(Suppl B):4853.
[20] Jault F, Gandjbakhch I, Rama A, et al. Active native valve endocarditis: determinants of
operative death and late mortality. Ann Thorac Surg 1997;63:173741.
[21] Larbalestier R, Kinchla N, Aranki S, et al. Acute bacterial endocarditis: optimizing
surgical results. Circulation 1992;86(SII):6874.
[22] Middlemost S, Wisenbauch T, Meyerowitz NC, et al. A case for early surgery in native left
sided endocarditis complicated by heart failure: results in 203 patients. J Am Coll Cardiol
1991;18:6637.
[23] Rocchioli C, Chastre J, Lecompte Y, et al. Prosthetic valve endocarditis. The case for
prompt surgical management. J Thorac Cardiovasc Surg 1986;92:7849.
gostino RS, Miller DC, Stinson EB. Valve replacement in patients with native valve
[24] dA
endocarditis: what really determines operative outcome? Ann Thorac Surg 1985;40:42938.
[25] Soma Y, Handa S, Iwanaga S. Medical treatment or surgical intervention? A cooperative retrospective study on infective endocarditistiming of operation. Jpn Circ J 1991;55:
799803.
[26] Bayer AS, Bolger AF, Taubert KA, et al. Diagnosis and management of infective endocarditis and its complications [AHA scientic statement]. Circulation 1998;98:293648.
[27] Croft CH, Woodward W, Elliot A, et al. Analysis of surgical versus medical therapy in
active complicated native valve endocarditis. Am J Cardiol 1983;51:16505.
[28] Grin FM, Jones G, Cobbs CG. Aortic insuciency in bacterial endocarditis. Ann Intern
Med 1972;76:238.
[29] Mills J, Utley J, Abbott J. Heart failure in infective endocarditis. Predisposing factors,
course and treatment. Chest 1974;66:1517.
[30] Richardson JV, Karp RB, Kirklin JW, et al. Treatment of infective endocarditis: a 10-year
comparative analysis. Circulation 1978;58:58997.
[31] Alestig K, Hogevik H, Olaison L. Infective endocarditis: a diagnostic and therapeutic
challenge for the new millenium. Scand J Infect Dis 2000;32:34356.
[32] Choussat R, Thomas D, Isnard R, et al. Perivalvular abscesses associated with endocarditis: clinical features and prognostic factors of overall survival in a series of cases.
Perivalvular abscesses French multicentre study. Eur Heart J 1999;20:1701.
[33] Daniel W, Mugge A, Martin R, et al. Improvement in the diagnosis of abscesses associated with endocarditis by transesophageal echocardiography. N Engl J Med 1991;324:
795800.
[34] Erbel R, Rohmann S, Drexler M, et al. Improved diagnostic value of echocardiography in
patients with infective endocarditis by transesophageal approach: a prospective study. Eur
Heart J 1988;9:4353.
[35] Rohman S, Seifert T, Erbel R, et al. Identication of abscess formation in native-valve
infective endocarditis using transesophageal echocardiography: implications for surgical
treatment. Thorac Cardiovasc Surg 1991;39:27380.
[36] Pettersson G, Carbon C. The Endocarditis Working Group of the International Society of
Chemotherapy. Recommendations for the surgical treatment of endocarditis. Clin
Microbiol Infect 1998;4:3S3446.
[37] Omari B, Shapiro S, Ginzton L, et al. Predictive risk factors for periannular extension
of native valve endocarditis: clinical and echocardiographic analyses. Chest 1989;96:
12739.

474

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

[38] Blumberg EA, Karalis DA, Chandrasekaran K, et al. Endocarditis-associated paravalvular abscesses: do clinical parameters predict the presence of abscess? Chest 1995;107:
898903.
[39] Baumgartner FJ, Omari BO, Robertson JM, et al. Annular abscesses in surgical
endocarditis: anatomic, clinical, and operative features. Ann Thorac Surg 2000;70:4427.
[40] Knosalla C, Weng Y, Yankah AC, et al. Surgical treatment of active infective aortic valve
endocarditis with associated periannular abscess11 year results. Eur Heart J 2000;21:
4907.
[41] Lerakis S, Robert Taylor W, Lynch M, et al. The role of transesophageal echocardiography in the diagnostic management of patients with aortic perivalvular abscesses. Am J
Med Sci 2001;321:1525.
[42] Truninger K, Attenhofer Jost CH, Seifert B, et al. Long term follow up of prosthetic valve
endocarditis: what characteristics identify patients who were treated successfully with
antibiotics alone? Heart 1999;82:71420.
[43] Vlessis AA, Hovaguimian H, Jaggers J, et al. Infective endocarditis: ten-year review of
medical and surgical therapy. Ann Thorac Surg 1996;61:121722.
[44] Steckelberg JM, Murphy JG, Ballard D, et al. Emboli in infective endocarditis: the
prognostic value of echocardiography. Ann Intern Med 1991;114:63540.
[45] De Castro S, Magni G, Beni S, et al. Role of transthoracic and transesophageal
echocardiography in predicting embolic events with active infective endocarditis involving
native cardiac valves. Am J Cardiol 1997;80:10304.
[46] Di Salvo G, Habib G, Pergola V, et al. Echocardiography predicts embolic events in
infective endocarditis. J Am Coll Cardiol 2001;37:106976.
[47] Heinle S, Wilderman N, Harrison K, et al. Value of transthoracic echocardiography in
predicting embolic events in active infective endocarditis. Am J Cardiol 1994;74:799801.
[48] Heiro M, Nikoskelainen J, Engblom E, et al. Neurologic manifestations of infective
endocarditis. A 17-year experience in a teaching hospital in Finland. Arch Intern Med
2000;160:27817.
[49] Rohman S, Erbel R, Gorge G, et al. Clinical relevance of vegetation localization by
transesophageal echocardiography in infective endocarditis. Eur Heart J 1992;13:44652.
[50] Werner GS, Schulz R, Fuchs JB, et al. Infective endocarditis in the elderly in the era of
transesophageal echocardiography: clinical features and prognosis compared with younger
patients. Am J Med 1996;100:907.
[51] Olaison L, Hogevik H, Alestig K. Fever, C-reactive protein and other acute phase reactants
during treatment of infective endocarditis. Arch Intern Med 1997;157:88592.
[52] Olaison L, Belin L, Hogevik H, et al. Incidence of betalactam-induced delayed
hypersensitivity and neutropenia during treatment of infective endocarditis. Arch Intern
Med 1999;159:60715.
[53] Moyer D, Edwards JE. Fungal endocarditis. In: Kaye D, editor. Infective endocarditis.
New York: Raven Press; 1992. p. 299312.
[54] Nguyen MH, Nguyen ML, Yu VL, et al. Candida prosthetic valve endocarditis: prospective
study of six cases and review of the literature. Clin Infect Dis 1996;22:2627.
[55] Wieland M, Lederman MM, Kline-King C, et al. Left-sided endocarditis due to
Pseudomonas aeruginosa: a report of 10 cases and review of the literature. Medicine
(Baltimore) 1986;65:1809.
[56] Raoult D, Marrie T, Q fever. Clin Infect Dis 1995;20:48995.
[57] Levy PY, Drancourt M, Etienne J, et al. Comparison of dierent antibiotic regimens
for therapy of 32 cases of Q fever endocarditis. Antimicrob Agents Chemother 1991;35:
5337.
[58] Jacobs F, Abramowicz D, Vereerstraten P, et al. Brucella endocarditis: the role of
combined medical and surgical treatment. Rev Infect Dis 1990;12:7404.
[59] Calderwood SB, Swinski LA, Karchmer AW, et al. Prosthetic valve endocarditis. Analysis
of factors aecting outcome of therapy. J Thorac Cardiovasc Surg 1986;92:77683.

L. Olaison, G. Pettersson / Infect Dis Clin N Am 16 (2002) 453475

475

[60] Gordon SM, Serkey JM, Longworth DL, et al. Early onset prosthetic valve endocarditis:
the Cleveland Clinic experience 19921997. Ann Thorac Surg 2000;69:138892.
[61] Tornos P, Almirante B, Olona M, et al. Clinical outcome and long-term prognosis of late
prosthetic valve endocarditis: a 20-year experience. Clin Infect Dis 1997;24:3816.
[62] Yu VL, Fang GD, Keys TF, et al. Prosthetic valve endocarditis: superiority of surgical
valve replacement versus medical therapy only. Ann Thorac Surg 1994;58:10737.
[63] Jault F, Gandjbakheh I, Chastre JC, et al. Prosthetic valve endocarditis with ring abscesses.
Surgical treatment and long-term results. J Thorac Cardiovasc Surg 1993;105:110613.
[64] Lytle BW, Priest BP, Taylor PC, et al. Surgical treatment of prosthetic valve endocarditis.
J Thorac Cardiovasc Surg 1996;111:198207.
[65] Pansini S, di Summa M, Patane F, et al. Risk of recurrence after reoperation for prosthetic
valve endocarditis. J Heart Valve Dis 1997;6:847.
[66] Sett SS, Hudon MP, Jamieson WR, et al. Prosthetic valve endocarditis. Experience with
bioporcine prosthesis. J Thorac Cardiovasc Surg 1993;105:42834.
[67] Horstkotte D, Weist K, Ruden H. Better understanding of the pathogenesis of prosthetic
valve endocarditisrecent perspectives for prevention strategies. J Heart Valve Dis 1998;7:
3135.
[68] Eishi K, Kawazoe K, Kuriyama Y, et al. Surgical management of infective endocarditis
associated with cerebral complications. Multi-center retrospective study in Japan. J Thorac
Cardiovasc Surg 1995;110:174555.
[69] Gillinov AM, Shah RV, Curtis WE, et al. Valve replacements in patients with endocarditis
and acute neurologic decit. Ann Thorac Surg 1996;61:112530.
[70] Hart RG, KaganHallet K, Joerns SE. Mechanisms of intracranial hemorrhage in infective
endocarditis. Stroke 1987;18:104856.
[71] Ting W, Silverman N, Levitsky S. Valve replacement in patients with endocarditis and
cerebral septic emboli. Ann Thorac Surg 1991;51:1822.
[72] Matsushita K, Kuriyama Y, Sawada T, et al. Hemorrhagic and ischemic cerebrovascular
complications of active infective endocarditis of native valve. Eur Neurol 1993;33:26774.
[73] Parrino PE, Kron IL, Ross SD, et al. Does a focal neurologic decit contraindicate
operation in a patient with endocarditis? Ann Thorac Surg 1999;67:5964.
[74] Trouillet JL, Hoen B, Battik R, et al. Splenic involvement in infectious endocarditis.
Association for the Study and Prevention of Infectious Endocarditis. Rev Med Interne
1999;20:25863.
[75] Hogevik H, Olaison L, Anderson R, et al. Epidemiological aspects of infective endocarditis
in an urban populationa 5-year prospective study. Medicine (Baltimore);1995;74:32439.
[76] Faber M, FrimodtMoller N, Espersen F, et al. Staphylococcus aureus endocarditis in
Danish intravenous drug users: high proportion of left-sided endocarditis. Scand J Infect
Dis 1995;27:4837.
[77] Mathew J, Abreo G, Namburi K, Narra L, Franklin C. Results of surgical treatment for
infective endocarditis in intravenous drug users. Chest 1995;108:737.