Discussion
Infective endocarditis was first described by Osler, in 1857 as a
pathology of patients with a pre-existent valvular disease7. Since then, significant progress in disease
understanding has been achieved. The majority of large epidemiological
studies come, however, from developed countries, with a gap in solid
evidence from developing regions.
IE incidence varies from 2 to 6 cases per 100.000 inhabitants/year, a
value quite steady over the last decades 1. This
incidence, associated with prolonged hospital length of stay and
elevated hospitalization costs, makes IE a real worldwide burden8.
The present study provides valuable insights into IE in the current era,
bringing data from a tertiary hospital in South America, a complex
demographic region with huge contrasts and a lack of comprehensive
epidemiological reports.
In the present study, we demonstrated that the primary IE causative
organisms were Staphylococcus aureus, followed by
Enterococcus, Coagulase-negative staphylococci, and Viridans
streptococci. These findings are in accordance with the international
literature, which demonstrates a significant increase in Staphylococcus
aureus prevalence (21% - 30% in the last five decades)8, representing, currently, the most frequent
microbiological agent in high-income health systems. Besides, our
results are similar to the ones from other two Brazilian inquiries9, 10.
The transition in pathogen pattern, from viridans streptococcus to
Staphylococcus aureus, has been associated with population-aging,
decrease in rheumatic heart disease burden, and advanced device
management, particularly in cardiac patients 11, 12.
Precisely because of these factors, this transition was more pronounced
in high-income countries; however, as reported in this study, also in
less developed regions, Staphylococcus aureus has emerged as the primary
IE pathogen.
A common issue in IE studies from developing countries is the high
prevalence of negative blood cultures 2. In our study,
blood cultures were negative in 23.3% of cases, a value beyond the 10%
reported in recent scientific publications 12, 13, but
similar to other developing countries inquiries (10-55%)9, and even lower than in Asiatic populations
(30–65%) 14-16. Negative cultures are usually
related to infections with highly fastidious bacterial or non-bacterial
pathogens, inadequate microbiological technique, or prior administration
of antibiotics before the diagnosis of IE 17.
Most of our patients were males (66%) e the majority of the cases were
from native valves (73%), a similar pattern than that reported in other
studies from developing countries 10, 18-21. IE has a
well-recognized and consistent male predominance, with a reported male:
female ratio of 1.2:1 to 2.7:1 22. The explanation for
the male predominance could be related to the presence of congenital
cardiac conditions, such as a bicuspid aortic valve that also has a male
predominance 2.
Diverging from other developing countries reports, we observed a median
age of 60 years, resembling western countries trends, in which patients
age is typically 60 or 70 years old 23. According to
Yew SH et al., increased longevity, decreased rheumatic heart disease
incidence, staphylococci predominance, and increased use of invasive
procedures and medically implanted devices represent the current IE
scenario in developed countries 2. Taken these
features into consideration, our epidemiological and microbiological
profiles seem to be closer to those from developed countries instead of
developing regions. This pattern is also disclosed when we analyze the
most affected valve. While in developing countries, mitral valve
involvement predominates, due to a higher prevalence of rheumatic
disease 20, 24, 25, in our series, the aortic valve
was the most affected (54.5%).
In terms of mortality, despite improvements in diagnostic accuracy,
medical therapy, and surgical techniques, IE mortality rate remains
relatively high. In our study, we observed an overall in-hospital
mortality of 41.9%, meeting other Latin-American reports (46.4% and
31%) 9, 10, but much superior to that described in
high-income healthy systems (15 to 22%) 26. This
higher mortality rate may be justified by differences in patients’
profile, with a high prevalence of multiple comorbidities, and a delay
in reaching medical assistance. In our study, for instance, the average
time between symptoms onset and hospital admission was 7 days, resulting
in a remarkable diagnosis and intervention delay. Besides, 25% of our
patients were admitted on decompensated heart failure and 39%
presenting an embolic event.
Another relevant factor is that our study reflects data from a tertiary
referral center, which presents an inherent selection and referral bias.
As describe by the International Collaboration on Endocarditis –
Prospective Cohort Study (ICE-PCS), patients with IE who require surgery
and suffer complications (e.g., stroke, heart failure, and new valvular
regurgitation) are referred to tertiary hospitals more frequently than
those with an uncomplicated course 27, contributing to
increase the in-hospital mortality in referral centers.
In this same line, analyzing IE incidence and mortality in the Veneto
Region (Italy) from 2000 to 2008, Fedeli U et al. observed an increase
in 36-day mortality from 24.6 % (2000-2002) to 31.5 % (2006-2008),
which was, at least partially, attributed to a growing number of the
elderly patients (median age was 68 years) 28.
According to the present study, diabetes mellitus, previous structural
heart disease, and mitral valve infection were the independent
predictors of in-hospital mortality, while patients submitted to
surgical treatment had 55% less chance of dying than those handled just
with clinical treatment. This finding follows the new trends in IE
treatment, which suggests that early valve surgery will result in better
outcomes. Liang et al., for instance, conducted a meta-analysis
revealing that, compared with non-early surgery, early surgery was
associated with reduced in-hospital (OR 0.57) and long-term mortality
incidence (OR 0.57) 26.
Last but not least, 49% of our patients received a cardiac surgical
intervention, which fits the rate reported in the current IE European
guideline (40–50%). This guideline also reinforces that despite early
surgery is indicated to avoid progressive HF, irreversible structural
damage and to prevent systemic embolism, it is associated with
significantly higher risk. Therefore, surgical indication would be
justified in patients with high-risk features that make the possibility
of cure with antibiotic treatment unlikely, and who do not have comorbid
conditions or complications that make the prospect of recovery remote29.
Unfortunately, the present cohort had not enough power to compare those
patients that were submitted to an early intervention versus those that
had more delayed surgery. However, our study adds evidence in the
assumption that surgically treated patients have better outcomes than
those clinically managed.
The major limitation of our study is its retrospective and single-center
design, enrolling patients from a tertiary-care center, which could not
represent the profile of entire South American health system. On the
other hand, one of the major highlights of our study is that this is one
of the largest cohorts of patients from Latin America and the largest in
Brazil. It is also important to highlight that the description of
temporal trends and associations does not provide evidence of causality.
Despite a long-term enrollment period, this study focuses on short-term
results. Properly designed trials with long-term follow-up are required
to confirm the impact and trends in IE.