ADULT CARDIAC SURGERY:
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CARDIOVASCULAR
Surgical Management of Infective Endocarditis:
Early Predictors of Short-Term Morbidity and
Mortality
Davinder S. Jassal, MD, Tomas G. Neilan, MD, Aruna D. Pradhan, MD,
Karen E. Lynch, RN, Gus Vlahakes, MD, Arvind K. Agnihotri, MD, and
Michael H. Picard, MD
Cardiac Ultrasound Laboratory, Cardiology Division, Department of Medicine, and Cardiac Surgery Division, Department of
Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
Background. Infective endocarditis is a diagnostic and
therapeutic challenge that ultimately requires surgical
intervention in 20% of all cases. Early determinants of
morbidity and mortality in this high risk population are
not well described.
Methods. The aim of this study was to determine
preoperative clinical, microbiological, electrocardio-
graphic, and echocardiographic variables that predicted
the need for permanent pacemaker implantation and
in-hospital death in a surgical cohort of patients with
active infective endocarditis.
Results. We identified 91 patients (61 males and 30
females, mean age 58 16 years) who underwent surgical
intervention for active culture-positive infective endocardi-
tis as defined by the Duke criteria. Native valve infective
endocarditis was present in 78 (85.7%) and prosthetic valve
endocarditis in 13 (14.3%) of cases. The aortic valve was
A cute infective endocarditis (IE) is a clinical challenge
that is often associated with high patient morbidity
and mortality [1]. Despite appropriate antibiotic use, surgi-
cal intervention is required in 20% of cases [2]. Among
patients who undergo surgical intervention, 10% require
permanent pacemaker implantation [2].
The indications for surgery in IE have continued to
evolve, but frequently include intractable heart failure,
abscess formation, recurrent embolic events, organism in-
volved, and presence of prosthetic material [3 8]. While
mortality has improved from 30% to 15% over the past two
decades, it remains substantial [1].
With increasing demands for surgery in patients with IE the
identification of preoperative variables that may identify the
Accepted for publication Feb 6, 2006.
Address correspondence to Dr Jassal, Department of Cardiology, Cardiac
Ultrasound Laboratory, Massachusetts General Hospital, Harvard Med-
ical School, VBK-508, 55 Fruit Street, Boston, MA 02114; e-mail:
djassal@partners.org.
2006 by The Society of Thoracic Surgeons
Published by Elsevier Inc
infected in 61 (67.0%), the mitral in 35 (38.5%), and multiple
valves in 8 patients (8.8%). The most common indication for
surgical intervention was intractable heart failure. Twenty-
two patients (24.2%) required pacemakers, while there were
14 (15.4%) in-hospital deaths. In age-adjusted and gender-
adjusted analyses, the presence of left bundle branch block
on preoperative electrocardiogram (ECG) and presence of
depressed left ventricular systolic function (ejection frac-
tion [EF] < 50%) predicted the need for a permanent
pacemaker implantation, while the presence of depressed
left ventricular function predicted in-hospital mortality.
Conclusions. Preoperative ECG findings of left bundle
branch block and reduced left ventricular function may allow
for early risk stratification of this high risk population.
(Ann Thorac Surg 2006;82:5249)
2006 by The Society of Thoracic Surgeons
highest risk patients in this surgical cohort would be clinically
useful. Although prior studies have evaluated clinical, micro-
biological, and echocardiographic (Echo) predictors of short-
term outcomes in patients with acute IE [913], little is known
about early determinants of outcomes in the current era
among high-risk surgically treated cohorts [1418] and we
have found no studies that have examined factors associated
with the need for pacemaker implantation.
We thus sought to evaluate the impact of preoperative
clinical variables including the Duke criteria for IE, preop-
erative ECG, and echocardiographic findings on short-term
morbidity and mortality in patients surgically managed for
endocarditis.
Patients and Methods
From 1995 to 2004 inclusive, 637 patients were identified
with acute infective IE at the Massachusetts General Hos-
pital. Of this population, 91 consecutive patients having
undergone valve replacement for acute culture-positive IE
0003-4975/06/$32.00
doi:10.1016/j.athoracsur.2006.02.023
Ann Thorac Surg JASSAL ET AL 525
2006;82:524 9 PROGNOSIS IN INFECTIVE ENDOCARDITIS

Table 1. Clinical Characteristics of Total Population and According to Survival

Survived Died Total Population
Characteristics (n 77) (n 14) (n 91) p Value

Age (years) 56.6 (16.0) 63.6 (13.6) 57.7 (15.8) 0.13

CARDIOVASCULAR
Male gender 54 (70.1) 7 (50.0) 61 (68.1) 0.13
Diabetes mellitus 8 (10.4) 1 (7.1) 9 (9.9) 1.00
IVDU 9 (11.7) 1 (14.3) 11 (12.1) 0.68
Prior CABG 10 (13.0) 1 (7.1) 11 (12.1) 1.00
CAD 17 (22.1) 2 (14.3) 19 (20.9) 0.73
NVE 66 (85.7) 12 (85.7) 78 (85.7) 1.00
PVE 11 (14.3) 2 (14.3) 13 (14.3) 1.00
Microorganism
S. aureus 21 (27.3) 5 (35.7) 26 (28.6) 0.53
Virdians streptococci 31 (40.3) 5 (35.7) 36 (39.6) 1.00
Gram negative 12 (15.6) 0 (0) 12 (13.2) 0.20
Other 15 (19.5) 4 (28.6) 19 (20.9) 0.48
Transesophageal echo
TEE vegetation 61 (83.6) 12 (85.7) 73 (83.9) 1.00
TEE abscess 22 (30.1) 6 (42.9) 28 (32.2) 0.36
Aortic valve 53 (68.8) 8 (57.1) 61 (67.0) 0.54
Mitral valve 31 (40.3) 4 (28.6) 35 (38.5) 0.55
Tricuspid valve 1 (1.3) 2 (14.3) 3 (3.3) 0.06
Multiple valves 8 (10.4) 0 (0) 8 (8.8) 0.35

Values are n (%) or mean SD. p values were calculated by the t test for difference in means and the Fisher exact test for difference in proportions.
CABG coronary artery bypass grafting; CAD coronary artery disease; IVDU intravenous drug user; NVE native valve endocarditis;
PVE prosthetic valve endocarditis; TEE transesophageal echo.

were identified from a computer registry database of car-
diac surgical patients. The database captured detailed in-
formation on a wide range of preoperative, intraoperative,
and postoperative variables for all patients undergoing
cardiac surgery at this tertiary care center. The study pro-
tocol was approved by the local institutional review board
on Aug 16, 2004 and individual patient consent was waived.
In addition to data that was available through the data-
base, the medical records of all 91 patients were extensively
reviewed. Preoperative clinical variables of interest in-
cluded age, gender, diabetes, Duke criteria for infective
endocarditis, infecting microorganism, and indication for
surgery. Intraoperative variables of interest included the
number and type of valves infected, intraoperative patho-
logical findings, and surgical procedure performed. Postop-
erative variables that were considered included need for
transfusion (2 units of packed red blood cells), prolonged
ventilation greater than 24 hours, cerebrovascular accident,
need for dialysis, permanent pacemaker implantation, rate
of reoperation, and in-hospital mortality. Need for postop-
erative permanent pacemaker implantation and in-hospital
death were the short-term clinical outcomes of interest.
Preoperative ECG and echocardiography were evaluated
in all 91 patients. Conduction abnormalities including first-
degree block, interventricular conduction delay (defined as
QRS 120 msec), right bundle branch block (RBBB), and
left bundle branch block (LBBB) were recorded. Right
bundle branch block was defined as: (1) QRS 120 msec; (2)
rsR pattern in lead V1 or V2; and (3) S wave longer than
duration of the R wave in leads V6 and I. Left bundle branch
block was defined as: (1) QRS 120 msec; (2) broad and
notched R waves in leads V5, V6, and aVL; (3) absent Q
wave in left-sided leads; and (4) R wave 60 msec in leads
V5 and V6. During the study period, all 91 patients had a
preoperative transthoracic echocardiogram (TTE), 80 pa-
tients had a preoperative transesophageal echocardiogram
(TEE), and 85 patients had an intraoperative TEE. Echocar-
diographic parameters of interest included the presence of
vegetation, maximum length of vegetation, abscess, fistula
formation, infected valve, left atrial dimension (anterior-
posterior measurement in the parasternal long axis), left
ventricular cavity dimensions, and ejection fraction (EF). An
EF of 0.50 was defined as normal.
The data are summarized as mean SD or number
(percentage). Univariable analyses were conducted using
the t test for comparison of means between groups and the
Fisher exact test for comparison of categoric parameters.
Multivariable models were constructed using stepwise lo-
gistic regression with an entry probability criterion of 0.20
and stay criterion of 0.10, in order to identify preoperative
characteristics that were independently associated with the
two endpoints of postoperative permanent pacemaker im-
plantation and in-hospital death. Age and gender were
forced into both statistical models. Kaplan-Meier survival
curves were constructed for postoperative survival by cat-
egory of left ventricular (LV) dysfunction. The log-rank test
was used to assess differences in postoperative survival.
The Statistical Analysis System (SAS Institute, Cary, NC)
8.01 was used to perform the analysis.
 526 JASSAL ET AL Ann Thorac Surg
PROGNOSIS IN INFECTIVE ENDOCARDITIS 2006;82:524 9

Table 2. Indications for Surgery

Survived Died Total Population
Characteristics (n 77) (n 14) (n 91) p Value

Heart failure 68 (88.3) 12 (92.9) 81 (89.0) 1.00

CARDIOVASCULAR

Abscess 22 (30.1) 6 (42.9) 28 (32.2) 0.36

Emboli 5 (6.5) 1 (7.1) 6 (6.6) 1.00
Fungal endocarditis 3 (3.9) 1 (7.1) 4 (4.4) 0.49

Values are n (%). p values were calculated by the Fisher exact test.

Results resection of the infected tissue followed by either valve

There were 61 men and 30 women averaging 58 16 years of
age with a diagnosis of culture positive active IE as defined by
the Duke criteria (Table 1). Of the 91 patients requiring
surgical intervention, the majority of patients (85.7%) were
diagnosed with native valve endocarditis (NVE). The aortic
valve was most commonly infected in 61 (67.0%) patients
followed by the mitral valve in 35 (38.5%) patients. As shown
in Table 1, there was no difference in preoperative clinical
characteristics between patients who survived compared with
patients who died (in-hospital mortality rate 15.4%).
The most common offending pathogen for both NVE and
prosthetic valve endocarditis (PVE) was Streptococcus viri-
dans followed by Staphylococcus aureus (Table 1). These two
organisms accounted for approximately 75% of NVE cases.
The virulent nature of S. aureus may account for the high
proportion of patients found to have abscesses intraopera-
tively ( 30%) in our series. Staphylococcus epidermidis was
identified in only three cases of PVE.
Indications for surgical intervention included new severe
valvular regurgitation with heart failure, intracardiac ab-
scesses, recurrent embolic events, and fungal endocarditis
(Table 2). The most common echocardiographic finding
leading to surgical treatment for both NVE and PVE was
severe valvular regurgitation with intractable heart failure
in 81 (89.0%) patients.
All 91 patients underwent cardiopulmonary bypass with
repair or replacement. The choice between biological or
mechanical prosthesis was made according to established
guidelines, the patients age, the need for long-term anti-
coagulation, and both surgeon and patient preference.
Fifty-eight patients underwent replacement with a biopros-
thesis, either a pericardial tissue valve (3) or homograft
valve (55), while 22 patients underwent replacement with a
mechanical valve (Table 3). Only 11 patients underwent
valve repair in our surgical series (aortic valve [n 6],
mitral valve [n 4], and tricuspid valve [n 1]). Concom-
itant coronary artery bypass grafting was performed in 11
patients. The mean perfusion time and cross-clamp times
for the total population were 171 45 minutes and 131 38
minutes, respectively.
The postoperative clinical events are shown in Table 4.
Overall, the rates of postoperative stroke, requirement for
dialysis, and reoperation rate were less than 10%. The need
for blood transfusion (greater than two units of packed red
blood cells), prolonged ventilation as defined greater than
24 hours, and need for permanent pacemaker were signif-
icantly higher in patients who died compared with those
who survived (p 0.05). The need for permanent pace-
maker implantation in the entire cohort was 24% (n 22).
Seventeen of these 22 patients had an aortic valve replace-
ment and 5 patients had a mitral valve replacement. Addi-
tionally, of these 22 patients 15 had third-degree block and

Table 3. Intraoperative Data

Survived Died Total Population
(n 77) (n 14) (n 91) p Value

Intraoperative findings
Vegetation 77 (100.0) 13 (92.9) 90 (98.9) 0.55
Abscess 22 (28.6) 5 (35.7) 27 (29.7) 0.75
Leaflet perforation 4 (5.2) 0 (0) 4 (4.4) 1.00
Fistula 1 (1.3) 0 (0) 1 (1.1) 1.00
Surgical procedure
Bioprosthesis
Carpentier-Edward 3 (3.9) 0 (0) 3 (3.3) 1.00
homograft 45 (58.4) 10 (71.4) 55 (60.4) 0.55
Mechanical prosthesis 22 (28.6) 0 (0) 22 (24.2) 0.019
Tissue repair 7 (9.1) 4 (28.6) 11 (12.0) 0.025
CABG 10 (13.0) 1 (7.1) 11 (12.0) 1.00
Cross-clamp time (min) 131 38 125 46 126 44 0.45
Perfusion time (min) 171 45 167 53 168 52 0.65

Values are n (%). p values were calculated by the t test for difference in means and the Fisher exact test for difference in proportions.
Ann Thorac Surg JASSAL ET AL 527
2006;82:524 9 PROGNOSIS IN INFECTIVE ENDOCARDITIS

Table 4. Postoperative Clinical Events

Survived Died Total Population
Clinical Event (n 77) (n 14) (n 91) p Value

Transfusion (2 units RBC) 7 (9.1) 5 (35.7) 12 (13.2) 0.02

CARDIOVASCULAR
Ventilation 24 hours 10 (13.0) 9 (64.3) 19 (20.9) 0.001
Total ICU stay (hours) 120 45 110 55 115 53 0.45
Cerebrovascular accident 3 (3.9) 2 (14.3) 5 (5.5) 0.17
Hemodialysis 4 (5.2) 2 (14.3) 6 (6.6) 0.23
Permanent pacemaker 15 (19.5) 7 (50.0) 22 (24.2) 0.04
Reoperation (for bleeding) 1 (6.5) 1 (14.3) 2 (2.2) 0.29
Reoperation (for valve) 4 (5.2) 1 (14.3) 5 (5.5) 0.35
LOS 30 days 20 (26.0) 5 (35.7) 25 (27.5) 0.52

Values are n (%) or mean. p values were calculated by the t test for difference in means and the Fisher exact test for difference in proportions.
ICU intensive care unit; LOS length of stay; RBC red blood cell.

7 had Mobitz type II second-degree block after surgery,
prior to permanent pacemaker implantation.
As shown in Table 5, several preoperative ECG variables
including first-degree block, interventricular conduction
delay greater than 120 msec, and LBBB predicted the need
for permanent pacemaker implantation on univariate anal-
ysis. Using a stepwise selection algorithm for model build-
ing with inclusion of age and gender, LBBB (p 0.001) and
low preoperative EF (p 0.008) were the only independent
predictors of pacemaker implantation.
After age and gender adjustment, a preoperative EF
less than 50% independently predicted mortality with a
sensitivity of 92.3% and specificity of 95.7% (Tables 6, 7;
Fig 1). The mean EF in those patients who died was 36
7%. The presence of vegetation, size of vegetation, ab-
scess, left atrial dilatation, and LV enlargement were not
univariate predictors of in-hospital death.
Comment
The prompt identification of patients at high risk of develop-
ing complications, prolonged hospitalization, or death is im-
portant in the management of IE. The observation from this
study is that simple preoperative cardiac investigations may
allow the clinician to determine which patients may experi-
ence poor short-term clinical outcomes after surgery. A pre-
operative ECG demonstrating LBBB and a preoperative echo-
cardiogram demonstrating LV dysfunction are independent
predictors for the need for a permanent pacemaker postoper-
atively and in-hospital death, respectively.
High degree atrioventricular block occurs in 2% to 4% of all
cases of infective endocarditis, carrying an increased risk of
heart failure and death [2]. Conduction abnormalities are an
early indication of an infectious process extending to involve
the membranous interventricular septum, often a local exten-
sion of aortic valve endocarditis. If the infectious process
enters the triangle of Koch, inflammation or destruction of the
atrioventricular node and bundle of His will result in heart
block. Previous studies on the permanent pacemaker require-
ments for patients with active IE are limited. Delay and
colleagues [19] reported that permanent pacemaker implan-
tation for atrioventricular block was a common complication
after both NVE and PVE (12% to 15%). No correlation between
preoperative ECG and subsequent pacemaker requirement
was reported. The incidence of permanent pacemaker re-
quirement in our population was somewhat higher at 24%.
This difference probably reflects the high risk nature of the
patients in a tertiary care setting.
The present study correlates preoperative ECG evidence of
conduction disease with the requirement for permanent pac-
ing in patients surgically managed for IE. Although the pres-
ence of LBBB had a low sensitivity of 40.9%, the specificity
98.5%, positive predictive value 90.0%, and negative predictive
value 83.3% were high for subsequent permanent pacemaker
insertion. In a cohort of patients with underlying LBBB and no
structural heart disease, the incidence of developing progres-
sive complete heart block is 1% to 2% [20]. In patients under-
going surgical debridement of the infectious nidus in the
setting of structural heart disease, it is not unexpected to
observe a high incidence of pacing requirements postopera-
tively as seen in our series. One year follow-up of ECGs in

Table 5. Preoperative Electrocardiographic Variables Associated with Pacemaker Implantation

No Pacemaker Yes Pacemaker
Variable (n 69) (n 22) p Value

First Degree AVB 12 (19.4) 15 (68.2) 0.001

QRS 120 msec 12 (18.2) 13 (59.1) 0.001
RBBB 3 (4.6) 3 (13.) 0.16
LBBB 1 (1.5) 9 (40.9) 0.001

Values are n (%) or mean. p values were calculated using the Fisher exact test.
AVB atrioventricular block; RBBB right bundle branch block; LBBB left bundle branch block.
 528 JASSAL ET AL
PROGNOSIS IN INFECTIVE ENDOCARDITIS
Table 6. Echo Variables Associated With In-Hospital Death
Survived
Variable (n 77)
Vegetation length (10 mm) 20 (30.0)
CARDIOVASCULAR
LAE (LA 38 mm) 54 (77.1)
LVE (LVID 53 mm) 33 (47.1)
EF 50% 3 (4.3)
Values are n (%). p values were calculated using the Fisher exact test.
EF ejection fraction; LA left atrium; LAE left atrial enlargement;
end-diastolic diameter.
those patients requiring a permanent pacemaker postopera-
tively demonstrated that 90% had persistent advanced con-
duction abnormalities requiring pacing needs, reflecting the
aggressive nature of the initial infective process. Of interest,
although progressive conduction disease on serial ECGs
serves as a marker of extension of the infectious process [2],
neither aortic valve endocarditis nor the presence of an ab-
scess in our population were independent predictors of pacing
requirements postoperatively.
Reduced LV function on preoperative echocardiography
served as an independent prognostic marker for in-hospital
mortality. Echocardiography is the primary technique for
the detection of vegetations and cardiac complications re-
sulting from IE [21]. Echocardiography provides one of the
major Duke criteria [3]. Three echocardiographic findings
are considered to be major criteria for the diagnosis of
endocarditis: (1) presence of vegetations defined as mobile
echodense masses implanted in a valve or mural endocar-
dium; (2) presence of abscess; or (3) presence of a new
dehiscence of a valvular prosthesis [3, 22]. With the devel-
opment of TEE imaging, the noninvasive detection of veg-
etations has substantially improved [23, 24].
Although echocardiography is widely used in the diagnosis
and prognosis of IE, there is little available data regarding its
ability to predict outcomes in the surgical cohort of patients
with endocarditis. Wallace and colleagues [25] evaluated a
number of clinical predictors of outcome in patients with
infective endocarditis; and of interest, patients with poor LV
function defined by echocardiography did not have a higher
mortality at discharge or 6 month follow-up. Di Salvo and
colleagues [26] clearly demonstrated that the presence and
characteristics of vegetations on TEE is predictive of embolic
events in patients managed for IE, but no evaluation of
preoperative LV function and subsequent in-hospital mortal-
ity was reported. Recently, Thuny and colleagues [27] demon-
strated that vegetation length greater than 15 mm was a strong
predictor (relative risk 2.1; 95% confidence interval [CI], 1.34
Table 7. Predictive Accuracy of Preoperative EF for Postoperative Death
EF Cutpoint Prevalence Sensitivity
35% 6 (6.6) 46.2
40% 7 (7.7) 53.9
50% 15 (16.4) 92.3
Values are n (%).
EF ejection fraction; NPV negative predictive value; PPV positive predictive value.
Ann Thorac Surg
2006;82:524 9
Died Total Population
(n 14) (n 91) p Value
4 (28.6) 24 (26.4) 0.95
11 (84.6) 65 (78.3) 0.73
6 (46.2) 39 (47.0) 1.00
12 (92.3) 15 (18.1) 0.001
LVE left ventricular enlargement; LVID left ventricular
to 3.26; p 0.001) of one year mortality in patients with
endocarditis, but again no correlation between baseline LV
function and mortality was reported.
A preoperative LV ejection fraction less than 0.50 in our
patient population was an independent predictor of in-
hospital mortality. The presence of a preoperative EF less than
0.50 had high sensitivity 92.3%, specificity 95.7%, PPV 80%,
and NPV 98.5% for predicting in-hospital death. Other clinical
settings in which a reduced left ventricular ejection fraction
(LVEF) has clearly been demonstrated to have adverse prog-
nostic implications include postmyocardial infarction, chronic
heart failure due to ischemic or pre-coronary artery bypass
grafting or valvular surgery [2831]. The etiology of LV dys-
function in our patients, however, remained undefined.
Whether the patients LVEF less than 50% was preexisting
prior to developing infective endocarditis or whether the
reduction in overall LV function was a result of the acute
infectious process could not be adequately assessed.
In our series, age, surgery, S. aureus infection, pros-
thetic valve, abscess, or aortic valve endocarditis were not
significantly associated with mortality [9 19, 2527]. This
may reflect the changing spectrum of antibiotics, im-
proved detection of complications with TEE, earlier in-
tervention, and advances in surgical techniques. As the
disease and its management have developed over the
past decade, these variables may no longer be associated
with poor short-term outcomes in the current era.
The primary limitation of this study is the small sample
size and its retrospective nature. Even though this study
population represents one of the largest of its kind in the
current surgical management of IE [16 18], it remains small
enough to be interpreted with caution. A larger prospective
series or a multicentered approach may enable us to make
more substantive conclusions regarding the roles of preop-
erative ECG and echocardiography in determining out-
come measures in the surgical setting of active IE. In
addition, due to the long recruitment period of ten years in
Specificity PPV NPV
100 100 90.9
100 100 92.1
95.7 80 98.5
Ann Thorac Surg
2006;82:524 9
Fig 1. Kaplan-Meier survival curves according to preoperative ejec-
tion fraction (EF).
our study, surgical techniques and antimicrobial therapy
have evolved, opening the study to treatment biases. None-
theless, the indications for surgical intervention in infective
endocarditis remain unchanged.
Preoperative ECG findings of conduction disease and
reduced left ventricular function on echocardiography
are independent determinants of short-term morbidity
and mortality that may allow for early risk stratification of
this high risk population.
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