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Heart Online First, published on February 11, 2016 as 10.1136/heartjnl-2015-308589

Valvular heart disease

ORIGINAL ARTICLE

Early versus late surgical intervention or medical

management for infective endocarditis: a systematic
review and meta-analysis
Mahesh Anantha Narayanan,1 Touk Mahfood Haddad,1 Andre C Kalil,2
Arun Kanmanthareddy,3 Rakesh M Suri,4 George Mansour,1 Christopher J Destache,5
Janani Baskaran,6 Aryan N Mooss,3 Tammy Wichman,7 Lee Morrow,7
Renuga Vivekanandan8
Additional material is
published online only. To view
please visit the journal online
(http://dx.doi.org/10.1136/
heartjnl-2015-308589).
For numbered afliations see
end of article.
Correspondence to
Dr Mahesh Anantha
Narayanan, Department of
Internal Medicine, Creighton
University School of Medicine,
Omaha, NE 68154, USA;
mahesh_maidsh@yahoo.com
Received 2 September 2015
Revised 8 January 2016
Accepted 14 January 2016

ABSTRACT
Objective Infective endocarditis is associated with high
morbidity and mortality and optimal timing for surgical
intervention is unclear. We performed a systematic
review and meta-analysis to compare early surgical
intervention with conservative therapy in patients with
infective endocarditis.
Methods PubMed, Cochrane, EMBASE, CINAHL and
Google-scholar databases were searched from January
1960 to April 2015. Randomised controlled trials,
retrospective cohorts and prospective observational
studies comparing outcomes between early surgery at
20 days or less and conservative management for
infective endocarditis were analysed.
Results A total of 21 studies were included. OR of allcause mortality for early surgery was 0.61 (95% CI 0.50
to 0.74, p<0.001) in unmatched groups and 0.41 (95%
CI 0.31 to 0.54, p<0.001) in the propensity-matched
groups (matched for baseline variables). For patients
who had surgical intervention at 7 days or less, OR of
all-cause mortality was 0.61 (95% CI 0.39 to 0.96,
p=0.034) and in those who had surgical intervention
within 820 days, the OR of mortality was 0.64 (95%
CI 0.48 to 0.86, p=0.003) compared with conservative
management. In propensity-matched groups, the OR of
mortality in patients with surgical intervention at 7 days
or less was 0.30 (95% CI 0.16 to 0.54, p<0.001) and
in the subgroup of patients who underwent surgery
between 8 and 20 days was 0.51 (95% CI 0.35 to
0.72, p<0.001). There was no signicant difference in
in-hospital mortality, embolisation, heart failure and
recurrence of endocarditis between the overall
unmatched cohorts.
Conclusion The results of our meta-analysis suggest
that early surgical intervention is associated with
signicantly lower risk of mortality in patients with
infective endocarditis.

INTRODUCTION
To cite: Anantha
Narayanan M, Mahfood
Haddad T, Kalil AC, et al.
Heart Published Online First:
[please include Day Month
Year] doi:10.1136/heartjnl2015-308589

Infective endocarditis (IE) remains a major medical

illness with a high mortality approaching 50%1 secondary to complications including congestive heart
failure and neurological events.2 The American
College of Cardiology/American Heart Association
(ACC/AHA) endocarditis guidelines and the
European Society of Cardiology (ESC) Endocarditis
guidelines recommend specic parameters to be met

for performing early valve surgery.3 4 Indeed,

recommending early surgery is a class-IIa indication
for patients with recurrent emboli and persistent
vegetation;3 the European guidelines recommend
early surgery as a class-IIb indication for patients
with >1.5 cm vegetation.4 The decision to perform
early surgery has always been a challenge, considering the associated complications and unpredictable
response to antibiotic therapy. There are only a
limited number of randomised trials to compare the
effect of early surgery with conventional therapy.5
We performed a systematic review and meta-analysis
with available evidence to determine the benets,
risks and the optimal timing of early surgery in IE.

MATERIALS AND METHODS

Literature search
We performed an electronic search using the terms
early surgery, valve surgery, endocarditis, bacterial endocarditis and infective endocarditis
using PubMed, Cochrane, EMBASE, CINAHL and
Google-scholar databases for studies published
between January 1960 and April 2015, comparing
early valve surgery with conventional therapy for
IE. Studies included ranged from January 1996
to January 2015. The detailed search strategy
for PubMed is shown in online supplementary
appendix 1.
The systematic review and meta-analysis was performed according to the MOOSE (ResearchChecklist) guidelines.6 Search strategy is shown as
PRISMA owchart7 (gure 1). We also reviewed
the reference sections of all included studies,
review articles and editorials for completeness.
According to Cochrane guidelines, we excluded
conference abstracts. To evaluate the quality of
studies, we used the NewcastleOttawa scale8 (see
online supplementary table S1). We dened bestquality studies with a score of 9 (maximum), and
the highest-quality studies by a score of 8.

Eligibility criteria
Studies included should (1) be a randomised controlled trial, retrospective or prospective observational study; (2) compared two groups, one with
early valve surgery either at 20 days or less or during
initial hospitalisation, and the other with medical
therapy with or without late surgery; (3) included

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Valvular heart disease

Figure 1 PRISMA owchart.

only adult patients (excluded patients <16 years); (4) be published

in peer-reviewed literature and (5) be in English language.

Denitions
All-cause mortality was dened as death due to any cause at
follow-up. Early surgery was dened as surgery at 20 days or less
of diagnosis of IE or during initial hospitalisation. Conventional
therapy was dened as either medical therapy or late surgery (at
>20 days). We chose 20 days as cut-off since most studies comparing early surgery with conventional therapy had surgery performed within 3 weeks of diagnosis (see online supplementary
table S1). In the subgroup analysis, we compared all-cause mortality for (1) early surgery at 7 days or less with conventional
therapy and (2) early surgery between 8 and 20 days with conventional therapy. In the second subgroup analysis, we compared
all-cause mortality for surgery within a 20-day time period with
(1) surgery at greater than 20 days and to (2) medical therapy.

Data collection
We included patient demographics, sample size and type of
study in a structured abstract. Using a structured form, we
abstracted patient characteristics including setting, sample size,
proportion of cases undergoing valve surgery, mortality data
and risk estimates for different analyses. Two reviewers (MAN
and TMH) independently collected and abstracted the data after
reviewing full-text articles. Any initial disagreement was
reviewed and resolved by consensus.

Statistical analysis
Statistical analysis was performed using Comprehensive
Meta-analysis (CMA) (V.3.3.070). Categorical data were presented as odds ratio (OR) with 95% CIs using the random-effects
model for outcomes with different effect sizes. Early surgery was
considered as the experimental group and hence any OR <1
favours early surgery. Publication bias was analysed visually with
a funnel plot. Cochranes Q statistics were calculated and used to
determine the heterogeneity of included studies. I2 values of
25%, 50% and 75% were considered as low, moderate and high
heterogeneity, respectively.9 A sensitivity analysis was included
when necessary. A p value of <0.05 was considered signicant.

RESULTS
Study characteristics
Two independent reviewers (MAN and TMH) performed the
initial search (gure 1); and 1428 unique studies were identied
(see online supplementary appendix 1). Abstracts of these
studies were screened for eligibility and included in the analysis
after mutual consensus of the two reviewers. Finally, 21
studies5 1029 that met the eligibility criteria were included. A
total of 4797 patients underwent early surgery at 20 days or less
and 6251 patients received conventional therapy. Patient demographic data and baseline characteristics are shown in on-line
supplementary tables S1 and S2 respectively. Pooled OR of all
outcomes is summarised in table 1.

All-cause mortality of all included studies

Outcome
The studys primary end point was all-cause mortality. Secondary
end points included in-hospital death or 30-day mortality,
embolic events, heart failure and recurrence of endocarditis.

All-cause mortality was mentioned in 21 studies. In the group

that had early surgery, all-cause mortality was signicantly lower
than in the group without early surgical intervention (OR 0.61,
95% CI 0.50 to 0.74, p<0.001) (gure 2). Heterogeneity was

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Valvular heart disease

high among the included studies (I2=68%). Publication bias
assessed by the funnel plot showed minimal bias, with most
studies centred symmetrically at the top ( p=0.80) (see online
supplementary gure S1). A sensitivity analysis excluding the
study27 with maximum weight did not alter the results (OR
0.58, 95% CI 0.49 to 0.69, p<0.001). Another sensitivity analysis done by excluding studies with a low NewcastleOttawa
scale (7 or less) still showed odds favouring early surgical group
(OR 0.64, 95% CI 0.51 to 0.79, p<0.001).
Second, we categorised studies wherein surgery was performed
(1) at 7 days or less and (3) between 8 and 20 days and compared
these groups with conventional therapy (gure 3A, B). We chose
7-day time period as cut-off since previous data showed higher
risk of embolic events in the rst week after diagnosis of IE and
evidence showing failure of medical treatment for persistent bacteraemia after 1 week.3 30 Most studies included in the subanalysis were distributed around this number. All-cause mortality in
the group where surgery was performed at 7 days or less was estimated to be signicantly lower (OR 0.61, 95% CI 0.39 to 0.96,
p=0.034) when compared with conventional therapy. In the subgroup where surgery was performed at 820 days, odds of survival were still in favour of early surgery (OR 0.64, 95% CI 0.48
to 0.86, p=0.003) when compared with conventional therapy.
Third, in the subanalysis comparing early surgery (at 20 days
or less) with (1) late surgery (at >20 days) and (2) medical
therapy (gure 3C, D), all-cause mortality was lower with early
surgery when compared with late surgery (>20 days) but
without achieving a statistical signicance (OR 0.87, 95% CI
0.43 to 1.73, p=0.685). All-cause mortality was lower in the
early surgical group (OR 0.58, 95% CI 0.48 to 0.70, p<0.001)
when compared with medical therapy.
Only two studies15 26 reported isolated prosthetic valve endocarditis and analysis of these two studies showed lower odds of
all-cause mortality in the early surgical group (at 20 days or less)
when compared with conventional therapy without statistical
signicance (OR 0.80, 95% CI 0.48 to 1.34, p=0.404).
We did a subanalysis of studies to see if there was any trend in
mortality over the past 5 years (see online supplementary gure
S2) and OR was in favour of early surgery in studies both
before (OR 0.55, 95% CI 0.40 to 0.75, p<0.001) and after
(OR 0.66, 95% CI 0.52 to 0.85, p=0.001) the year 2010.

All-cause mortality of the propensity-adjusted groups

We performed an analysis with studies reporting outcomes using
a propensity-matched model. A total of 11 studies were
included and propensity-matched variables are mentioned in
online supplementary appendix 2. Again, all-cause mortality
was signicantly lower with early surgical intervention when
compared with conventional therapy (OR 0.41, 95% CI 0.31 to
0.54, p<0.001) (gure 4). Heterogeneity was moderate
(I2=41%). Sensitivity analysis performed by excluding study27
that contributed to maximum strength still showed lower mortality with early surgery (OR 0.40, 95% CI 0.29 to 0.55,
p<0.001). To eliminate bias, we also separated the studies
according to study type (see online supplementary gure S3).
Funnel plot of the included propensity-matched studies is
shown in online supplementary gure S4.
In the subgroup of studies wherein surgery was performed at
7 days or less, odds of mortality were again in favour of the early
surgical group (OR 0.30, 95% CI 0.16 to 0.54, p<0.001) (gure
5A) when compared with conventional therapy. There was a
similar mortality benet in the group that underwent surgery
between 8 and 20 days (OR 0.51, 95% CI 0.35 to 0.72, p<0.001)
when compared with conventional therapy (gure 5B). In the next
subgroup comparing early surgery at 20 days or less with (1)
medical therapy and (2) late surgery (>20 days) (gure 5C, D),
odds were in favour of early surgery when compared with both
late surgery (OR 0.35, 95% CI 0.16 to 0.76, p=0.008) and
medical therapy (OR 0.42, 95% CI 0.31 to 0.57, p<0.001).
Subgroup analysis of studies done before and after the year
2010 (see online supplementary gure S5) showed odds favouring early surgical group (OR 0.36, 95% CI 0.25 to 0.52,
p<0.001 and OR 0.49, 95% CI 0.35 to 0.67, p<0.001,
respectively). We also did an analysis excluding studies that mentioned early surgery at initial hospitalisation without mentioning the exact timing and that yielded similar OR favouring early
surgery (OR 0.62, 95% CI 0.50 to 0.78, p<0.001) (see online
supplementary gure S6).

In-hospital mortality
A total of 11 studies reported the incidence of in-hospital
mortality and there was no signicant difference between the
early surgery and conventional therapy (OR 0.82, 95% CI 0.58

Table 1 Summary of overall results from the analysis

Clinical end points (figure No.)
All-cause mortality in early surgery (at 20 days or less) vs Conventional therapy (2)
Early surgery at 7 days or less vs conventional therapy (3A)
Early surgery between 8 and 20 days vs conventional therapy (3B)
Early surgery at 20 days or less vs late surgery (at >20 days) (3C)
Early surgery at 20 days or less vs medical therapy (3D)
All-cause mortality in early surgery (at 20 days or less) vs Conventional therapy in
propensity-matched groups (4)
Early surgery at 7 days or less vs conventional therapy (propensity-matched) (5A)
Early surgery between 8 and 20 days vs conventional therapy (propensity-matched) (5B)
Early surgery 20 days or less vs late surgery (at >20 days) (propensity-matched) (5C)
Early surgery at 20 days or less vs medical therapy (propensity-matched) (5D)
In-hospital mortality in early surgery (at 20 days or less) vs Conventional therapy (6A)
In-hospital embolic events in early surgery (at 20 days or less) vs Conventional therapy (6B)
Heart failure at follow-up in early surgery (at 20 days or less) vs Conventional therapy (6C)
Recurrence of endocarditis in early surgery (at 20 days or less) vs Conventional therapy (6D)

Studies
included

OR (95% CI)

21
8
9
5
16
11

0.61
0.61
0.64
0.87
0.58
0.41

(0.50
(0.39
(0.48
(0.43
(0.48
(0.31

to
to
to
to
to
to

4
4
4
7
11
3
3
5

0.30
0.51
0.35
0.42
0.82
0.15
1.78
1.64

(0.16
(0.35
(0.16
(0.31
(0.58
(0.01
(0.47
(0.74

to
to
to
to
to
to
to
to

p Value

Heterogeneity

0.74)
0.96)
0.86)
1.73)
0.70)
0.54)

<0.001
0.034
0.003
0.685
<0.001
<0.001

I2=68
I2=61
I2=71
I2=70
I2=68
I2=41

0.54)
0.72)
0.76)
0.57)
1.16)
1.90)
6.74)
3.61)

<0.001
<0.001
=0.008
<0.001
0.270
0.142
0.394
0.219

I2=0
I2=0
I2=24
I2=50
I2=66
I2=77
I2=36
I2=32

Conventional therapy, Late surgery (at >20 days) or medical therapy.

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Valvular heart disease

Figure 2 Comparison of all-cause mortality between early surgery (at 20 days or less) and conventional therapy (late surgery at >20 days or
medical therapy).
to 1.16, p=0.270) (gure 6A). Sensitivity analysis with one
study27 removed (that had the maximum strength) yielded
similar results with no signicant difference in in-hospital mortality (OR 0.75, 95% CI 0.49 to 1.46, p=0.198).

embolic events between the early surgery versus conventional

therapy (OR 0.15, 95% CI 0.01 to 1.90, p=0.142).
Heterogeneity was high among the included studies (I2=77%).

Heart failure
In-hospital embolic events
Embolic events were reported in three of the included studies
(gure 6B). There was no signicant difference in the risk of

The incidence of heart failure was reported in only three studies

(gure 6C). Pooled OR did not show a signicant difference
between early intervention and conventional therapy (OR 1.78,

Figure 3 (A) Comparison of all-cause mortality between early surgery at 7 days or less and conventional therapy; (B) comparison of all-cause
mortality between early surgery at 820 days and conventional therapy; (C) comparison of all-cause mortality between early surgery (at 20 days
or less) and late surgery (at >20 days); (D) comparison of all-cause mortality between early surgery (at 20 days or less) and medical therapy.
4

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Valvular heart disease

Figure 4 Comparison of all-cause mortality between early surgery (at 20 days or less) and conventional therapy (late surgery at >20 days or
medical therapy) in propensity-matched studies.
95% CI 0.47 to 6.74, p=0.394). Heterogeneity was moderate
(I2=36%).

Recurrence of endocarditis at follow-up

Five studies reported recurrence of endocarditis at follow-up
(gure 6D) and heterogeneity was moderate among the
included studies (I2=32%). There was a higher trend of relapse
with early surgery without statistical signicance (OR 1.64,
95% CI 0.74 to 3.61, p=0.219).

DISCUSSION
IE is associated with high mortality and morbidity. The
in-hospital mortality rates vary from 15% to 20% and the
1-year mortality is estimated to be in the range of 30%
40%.3 31 Evidence regarding mortality benet from early surgical intervention is derived from a limited number of studies and
the approach is not without controversy. A meta-analysis32 from
2 years ago suggested the likelihood of benet from early
surgery in reducing mortality in IE but included a limited

Figure 5 (A) Comparison of all-cause mortality between early surgery at 7 days or less and conventional therapy in propensity-matched studies;
(B) comparison of all-cause mortality between early surgery at 820 days and conventional therapy in propensity-matched studies; (C) comparison of
all-cause mortality between early surgery (at 20 days or less) and late surgery (at >20 days) in propensity-matched studies; (D) comparison of
all-cause mortality between early surgery (at 20 days or less) and medical therapy in propensity-matched studies.
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Valvular heart disease

Figure 6 (A) Comparison of in-hospital mortality between early surgery (at 20 days or less) and conventional therapy; (B) comparison of
in-hospital embolic events between early surgery (at 20 days or less) and conventional therapy; (C) comparison of heart failure between early
surgery (at 20 days or less) and conventional therapy; (D) comparison of recurrence of endocarditis between early surgery (at 20 days or less)
and conventional therapy.
number of studies and did not comprehensively assess the
timing of surgical intervention and outcomes.
There has been no consensus on the optimal timing of early
surgery for IE. Guidelines recommend early surgery during
initial hospitalisation before completion of antibiotics.3
In our study, all-cause mortality was signicantly lower with
early surgery compared with conventional therapy, both in
unmatched and in propensity-matched groups. The results
remained unaltered after exclusion-sensitivity analyses.
Subgroup analysis of propensity-matched studies showed lower
odds of mortality in the group that underwent surgery at 7 days
or less (OR 0.30, 95% CI 0.16 to 0.54) when compared with
surgery at 820 days (OR 0.51, 95% CI 0.35 to 0.72); however,
the CIs overlap. The above observations were made in the
propensity-matched groups; in the unmatched groups, the OR
of mortality in the two subgroups of surgical intervention was
similar and better than conventional therapy. These ndings of
lower risk of mortality with early surgery are in contrast to the
belief that inammatory state increases the surgical mortality.
Hill et al17 in their study observed a fourfold increase in mortality in patients operated within 7 days of diagnosis of IE and was
attributed to severity of IE rather than timing of surgery.
When comparing early surgery to late surgery with medical
therapy in the propensity-matched groups, the OR was signicantly lower for early surgery indicating both late surgery and
medical therapy are inferior to early surgery. To evaluate the
effect of duration of follow-up on all-cause mortality, we
divided studies into shorter (1 year) and longer follow-up
studies (>1 year) and performed an exclusion-sensitivity analysis, which did not alter the results (see online supplementary
gure S7A,B). We attempted a meta-regression of follow-up
time and timing of surgery on all-cause mortality (see online
supplementary gure S8A,B) and the coefcient of regression
was 0.006 ( p=0.21) and 0.006 ( p=0.61), respectively, and so
were non-signicant. However, given the heterogeneous

comparators used and the variable timings reported by the original investigators of the included studies, the meta-regression
analysis cannot appropriately assess the impact of either
follow-up time or timing of surgery on all-cause mortality.
Embolisation33 and heart failure34 35 are the key contributors
to mortality in IE5 and so, mortality benet from early surgical
intervention is likely due to attenuation of these events.
In the study by Kang et al,5 embolic event rates were signicantly lower with early surgery (0% vs 21%, p=0.005).
All embolic events in the conservative management group
occurred within 6 weeks. Longitudinal follow-up at 6 months
showed mortality benet in the surgical group. Similarly, in
our study, there was a trend towards lower risk of embolic
events in the early surgical group (OR 0.15, 95% CI 0.01 to
1.90) without statistical signicance. Only 3 of the 21 studies
reported embolic events and so signicant inferences could
not be drawn. Further, improvements in surgical techniques,
operator experience and intensive postoperative care are likely
factors in decreasing mortality in patients who undergo early
surgery for IE. This could be seen from the consistently
favourable odds over the past 5 years (see online supplementary gure S5).
In our study, the in-hospital mortality was not different
between early surgery and conservative therapy similar to Kang
et al5 (3% vs 3%, p=1.00). We therefore think the mortality
benet is partially accrued from attenuation of embolic events.
In the International collaboration of endocarditis (ICE) prospective cohort study, it was shown that the highest risk of
embolism and death occured during the rst week after diagnosis of IE.30 The stroke rate was 4.82/1000 patient-days within
the rst week; this rate dropped by 65% during the second
week. We therefore believe the lower mortality in patients with
surgical intervention within the rst week as observed in our
study could partially be secondary to the decreased embolic
events following surgical intervention. Thus it could be seen

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that early surgery is benecial in improving long-term survival
without increasing short-term mortality.
Severity of heart failure has been shown to increase mortality
in IE.34 35 Hill et al17 suggested that surgical intervention
within 7 days likely decreased the incidence of heart failure.
This may be another reason for lower mortality in our subgroup
of patients who had surgery within 7 days. Though there was an
increasing trend of heart failure at follow-up with early surgical
intervention, it was statistically non-signicant. Also, only three
studies reported the incidence of heart failure and so strong
conclusions could not be derived from these data.
Incidence of prosthetic valve endocarditis ranges between
0.1% and 2.3% per year.36 There is a lack of consensus in the
management of patients with prosthetic valve endocarditis.3
Only two studies compared early surgery with conventional
therapy in isolated prosthetic valve infections.15 26 Pooled OR
showed mortality benet in the early surgical group without
statistical signicance. Since it is difcult to draw conclusions
based on these two studies, further randomised trials involving
prosthetic valves are needed.
There was a higher trend of recurrence of endocarditis in the
early surgical group, without statistical signicance. This trend
was largely inuenced by the study by Thuny et al,24 in which
8% of the patients, who underwent surgery within the rst
week, had recurrence, compared with only 2% of the patients,
who had surgery between 8 and 20 days ( p=0.02).24
A recent report by Chu et al29 showed that 24% of patients with
strong indications for surgery did not undergo surgical intervention
and patients with Staphylococcus aureus infection had a lower likelihoodofbeing operated.Infectionwith Saureushas beenshownto be
independently associated with neurological events.37 38 It could be
seen that S aureus wasthe major pathogen in a majorityof our studies
(seeonlinesupplementarytableS1)andsoearlysurgicalintervention
should be strongly recommended for these patients. Propensity
matching was done according to various micro-organisms (see
online supplementary appendix S2) and all-cause mortality was
better in the early surgical group. We therefore think that early
surgery may be benecial in patients with various micro-organisms
includingSaureus.
The recent 2015 ESC guidelines (Class-II, level of
evidence-B)4 and the 2014 AHA/ACC guidelines (Class-I, level
of evidence-B)3 recommend the timing of surgical intervention
be decided by a consensus of a multidisciplinary team involving
cardiologists, cardiothoracic surgeons, and infectious disease
specialists to reduce bias and provide best practices in patients
with IE. We agree with the above recommendations and think
that the Endocarditis team approach is the best strategy in
decreasing mortality and improving patient outcomes. One of
the recommendations is to perform early surgery for persistent
bacteraemia/fever for more than 57 days after initiation of antibiotic therapy (Class I, level of evidence B).3 According to our
analysis done from the available evidence, we suggest early
surgery at 7 days or less from diagnosis carries mortality benet
on a long term. Our analysis provides the most comprehensive
summary of the available literature to date until further randomised controlled trials become available.

LIMITATIONS
Our study has several limitations. First, our study was comprised
mainly of observational studies; and is therefore subject to the
individual limitations of the included studies. Secondly, all outcomes were not uniformly reported in the included studies, so
heterogeneity varied across different outcomes. Thirdly, individual studies mentioning prosthetic valve endocarditis, embolic
Anantha Narayanan M, et al. Heart 2016;0:18. doi:10.1136/heartjnl-2015-308589

events and heart failure were limited in number. Although propensity matching (see online supplementary appendix S2)
increased the strength of the study, sample sizes of the propensity matched studies were limited and there were inter-study variations in matching which could affect the results. We tried to
overcome some of these limitations by performing an exclusion
sensitivity analysis. In the absence of many randomised controlled trials, a meta-analysis like this provides evidence that is
less prone to type-1 error. Finally, baseline characteristics, surgical procedure, timing of procedure and follow-up times varied
across different studies.

CONCLUSION
Results of this meta-analysis suggest that early surgical intervention in IE increases survival when compared with conservative
management and/or delayed surgery. Our results further lend
support to the existing guidelines for early surgical intervention
in IE and emphasise the need to optimise the timing of surgery.
Further randomised studies are needed to validate these ndings.

Key messages
What is already known on this subject?
Infective endocarditis is associated with high morbidity and
mortality and the timing of surgery remains controversial.
What might this study add?
Our comprehensive systematic review and meta-analysis
suggests that early surgical intervention for infective
endocarditis reduces all-cause mortality when compared with
either delayed surgery or medical therapy. Further our study
assesses subgroup analysis of very early surgery and suggests
that this group of patients is more likely to have mortality
benet.
How might this impact on clinical practice?
The observations made in our study are in contrast to the
current clinical practice of delayed surgery in infective
endocarditis. Based on the mortality benets observed in our
study, medical practitioners may reconsider early surgery in
patients presenting with infective endocarditis.

Author afliations
1
Department of Internal Medicine, Creighton University School of Medicine, Omaha,
Nebraska, USA
2
Division of Infectious Diseases, University of Nebraska School of Medicine, Omaha,
Nebraska, USA
3
Division of Cardiology, Creighton University School of Medicine, Omaha, Nebraska,
USA
4
Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland,
Ohio, USA
5
School of Pharmacy & Health Professions and School of Medicine, Creighton
University, Omaha, Nebraska, USA
6
University of Texas Southwestern at Dallas, Dallas, Texas, USA
7
Division of Pulmonary Critical Care and Sleep Medicine, Creighton University School
of Medicine, Omaha, Nebraska, USA
8
Division of Infectious Diseases, Creighton University School of Medicine, Omaha,
Nebraska, USA
Acknowledgements The authors would like to acknowledge Mr Baskaran
Krishnamurthy for reviewing the manuscript for grammatical corrections.
Contributors Data access responsibility and analysis: all authors had full access to
all data in the study and take responsibility for the integrity of the data and the
accuracy of the data analysis. Study and concept design: MAN, RV, and RMS.
7

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Valvular heart disease

Acquisition of data: MAN, TMH, and GM. Analysis or interpretation of data, drafting
of the manuscript, administrative, technical or material support: all authors.

18
19

Competing interests CJD: Received grants from Cubist, Durata Therapeutics and
Forest labs. RMS: Research funding Edwards Lifesciences, St. Jude Medical and
Sorin Group. Current technology licensing agreements Sorin Group. Principle
InvestigatorNational PI FDA IDE PERCEVAL TrialSorin Group. Co-Investigator
PARTNER II, COAPT, SURTAVI and PORTICO. No personal nancial relationships with
industry.

20

Provenance and peer review Not commissioned; externally peer reviewed.

21
22

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Anantha Narayanan M, et al. Heart 2016;0:18. doi:10.1136/heartjnl-2015-308589

Downloaded from http://heart.bmj.com/ on February 11, 2016 - Published by group.bmj.com

Early versus late surgical intervention or

medical management for infective
endocarditis: a systematic review and
meta-analysis
Mahesh Anantha Narayanan, Toufik Mahfood Haddad, Andre C Kalil,
Arun Kanmanthareddy, Rakesh M Suri, George Mansour, Christopher J
Destache, Janani Baskaran, Aryan N Mooss, Tammy Wichman, Lee
Morrow and Renuga Vivekanandan
Heart published online February 11, 2016

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http://heart.bmj.com/content/early/2016/02/11/heartjnl-2015-308589

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Material http://heart.bmj.com/content/suppl/2016/02/11/heartjnl-2015-308589.
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