Revista Romn de Anatomie funcional i clinic, macro- i microscopic i de Antropologie

M.E. Hurmuzache
CLINICAL ANATOMY
Vol. X Nr. 4 2011

MAJOR COMPLICATIONS IN INFECTIVE ENDOCARDITIS

ANATOMOPATHOLOGIC ASPECTS OF TARGETED ORGANS
ON A COHORT OF 42 PATIENTS
M.E. Hurmuzache
University of Medicine and Pharmacy, Iasi, Romania
Faculty of Medicine
Department of Infectious Diseases
MAJOR COMPLICATIONS IN INFECTIVE ENDOCARDITIS ANATOMOPATHOLOGIC
ASPECTS OF TARGETED ORGANS ON A COHORT OF 42 PATIENTS (Abstract): Defined
as infection of the endocardial surface of the heart, infective endocarditis (IE) remains, despite
important advances in diagnosis and treatment, one of the most lifethreatening infection due to
various major cardiac and extracardiac complications. 42 patients with fatal IE were elected from
a cohort of 868 cases admitted between 1995 and 2008 in three hospital services in Iasi, Romania.
These patients had no known previous heart affections and had complete data regarding investigations, incriminated etiological agent and necroptic, micro-and macroscopic results. The central
aim of this retrospective study was to establish a correlation between data obtained and those
found in medical literature with possible particularities through unfavorable evolution in our area.
There were found some characteristics of the studied group related with age, type of endocarditis
(acute/subacute), major complications and changing in etiological spectrum (e.g. lower age of
death, still higher rate of fatal subacute IE, low rate of diagnosed previous heart disfunctions and
for cardiac surgery in complicated forms). Most affected organs, leading to fatal IE were heart,
brain and lungs, mostly due to embolization and infarcts. There was also observed higher rates in
mitral localization compared with data from literature and higher percents of death caused by
infarction. Correlation of data, obtained both intravitam and necroptic, should be useful for a
better monitoring of this severe disease. Key words: INFECTIVE ENDOCARDITIS, FATAL
COMPLICATIONS, ORGANS LESIONS

INTRODUCTION
Infective endocarditis (IE) is defined as an
infection of the endocardial surface of the
heart, which may include one or more heart
valves, the mural endocardium, or a septal defect. Its intracardiac effects include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial
abscesses and also possible a wide variety of
systemic signs and symptoms through several
mechanisms, including both sterile and infected
emboli and immunological phenomena (1,2).
Used terms in IE are as follow:
Native valve endocarditis (NVE), acute and
subacute
Prosthetic valve endocarditis (PVE) early
(up to 2 months after valve implantation)
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and late (until 12 months after valvuloplasty)

Intravenous drug abuse endocarditis (IVDA)
Pacemaker IE (PIE)
Nosocomial IE (NIE)/ Healthcare IE (HCIE)
IE develops most commonly on the mitral
valve, closely followed in descending order of
frequency by the aortic valve, the combined
mitral and aortic valve, the tricuspid valve and,
rarely, the pulmonic valve. Mechanical prosthetic and bioprosthetic valves exhibit equal
rates of infection. There is a commonly shared
process including bacteriemia (nosocomial or
spontaneous) that delivers the organisms to the
surface of the valve, adherence of the organisms and invasion of the valvular leaflets. The
common denominator for adherence and inva-

Major Complications in Infective Endocarditis Anatomopathologic Aspects of Targeted Organs

sion is nonbacterial thrombotic endocarditis, a

sterile fibrin platelet vegetation. The Venturi
effect explains why bacteria and fibrin-platelet
thrombus are deposited on the sides of the
low-pressure sink that lies just beyond a narrowing or stenosis. The development of subacute IE (3) depends on a bacterial inoculum,
sufficient to allow invasion of the preexistent
thrombus, critical mass being result of bacterial clumping produced by agglutinating antibodies. In acute IE (3), thrombus may be produced by the invading organism (most common
Staph.aureus, Streptococci A,C,G, Enterococci,
rarely gram-negative bacteria, HACEK, fungi)
affecting endothelial cells (endotheliosis) with
increases expression of adhesion molecules and
procoagulant activity on the cellular surface.
These microorganisms usually resist the bactericidal action of complement and possess fibronectin receptors for the surface of the fibrin-platelet thrombus. As the bacteria multiply,
surface of the vegetation is covered by ever-thickening layers of platelets and thrombin,
which protect them from neutrophils and other
host defenses. Organisms deep in the vegetation hibernate because of the paucity of available nutrients and are therefore less susceptible to bactericidal antimicrobials that interfere
with bacterial cell wall synthesis.
Complications of subacute IE (4,5) result
from embolization, slowly progressive valvular destruction and various immunological mechanisms. Many of the extracardiac manifestations of this form of IE are due to circulating
immune complexes (e.g. glomerulonephritis,
Osler nods, Roth spots). In acute IE (4,5) vegetations develop rapidly with no evidence of repair, producing spontaneous rupture of the leaflets, of the papillary muscles and of the chordae tendinae. In this case, complications result
from intracardiac disease and metastatic infection produced by suppurative emboli.
The following are potential complications
of IE (6):
cardiac : congestive heart failure; myocardial infarction; pericarditis; cardiac arrhythmia; cardiac valvular insufficiency;
aneurysm; myocardial/ring/intraventricular
abscesses
extra cardiac due to embolization, most
frequently in various territories
arterial emboli/infarcts

brain (stroke syndromes, cranial nerve palsies, mycotic aneurysms caused by weakening of the vessel walls and embolization of
vasa vasorum). The middle cerebral artery
is involved most often.
kidneys (glomerulonephritis, acute renal
failure)
rate (splenic abscess or infarct), pulmonary,
arthritis, myositis, bowel (mesenteric infarct)
Prognosis (7) largely depends on whether
or not complications develop. Untreated, IE is
generally fatal. Early detection and appropriate treatment can be lifesaving. Mortality is
largely various depending on etiological agent,
localization, age, complications and underlying diseases.
MATERIAL AND METHODS.
OBJECTIVES
42 patients with lethal IE elected from a
cohort of 868 cases of IE admitted in 3 hospital
services (Infectious Diseases Hospital, County
Universitary Hospital and Heart and Vessel
Institute) of the universitary town of Iasi, most
developed medical center in North Eastern part
of Romania, during a period of 14 years
(1995-2008). This retrospective study found
224 deaths (more than a quarter of the total
number of patients), 151 occurring in patients
with no previous known cardiac lesions and 73
in patients with different injuries of the heart.
The 42 patients choosed for this study are only
part from the 151 with unknown previous heart
illnesses. Selection was made among them, including for study only those cases in which
clinical data, investigations, etiological agent,
and anatomopathologic data were highly conclusive, allowing to obtain pertinent conclusions. The principal aim is finding a correlation between data obtained and those found
again in medical literature, with possible particularities through unfavorable evolution in our
area, related with age, etiology, endocardial
localization and major complications. The study
didnt approach epidemiological and therapeutically sides of infective endocarditis, the main
goal consisting in valvular localization and cardiac/extra cardiac complications, established
both intravitam (echocardiography, other imagistic investigations, intraoperatory exam) and
necroptic (macro- and microscopic).
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M.E. Hurmuzache

RESULTS
Regarding the age structure and sex ratio of
the focused group it was found a clear higher
prevalence of males (29 patients = 69%) and
patients over 50 years old. Correlated with age,
the study included:
4 young adults (<25 years, 3 males + 1
female)=9.5%
6 adults aged 25-35, 4 male and 2 female =
14.2%
14 adults 35-55 years old (10 male, 4 female)=33.3%
18 persons > 55 years (12 males, 6 females)=42.8%
Medium age of the group was 50.7 years.
No one of them was known with previous
important cardiac illnesses desirable for long
term treatment and surveillance. However, both
intravitam investigations and necroptic examination suggested different degrees of heart and
vessel modifications (ischemic, atherosclerotic,
cardiomiopathy) in more than 60% of patients
over 45 years old. There were reported also important associated illnesses (diabetus mellitus,
pulmonary, cholagenosis, tumors) in 16 cases
(38%) which represented high risk associated
factors for the evolution. Clinical and etiological features suggested acute IE in 38 cases
(90%) and subacute in 4 cases (10%). The way
IE evolved was clearly defined in almost 2/3 of
all cases commonly healthcare associated IE
(catheterism mostly) and 2 cases in young intravenous drug abusers. Microbiological agents
incriminated (positive blood cultures) were as
follow:
Staph. aureus 20 cases (47.6%)
Coagulazo negative Staph. 1 case (2.4%)
Streptococci (A,C,G) 4 cases (9.5%)
Enterococci 8 cases (19%)
Other (BGN, HACEK) 4 cases (9.5%)
Fungi 3 cases (7.1%)
Association bacteria fungi 2 cases (4.8%)
Diagnosis intravitam was established according to Duke modified major criteria, including at least 2 positive blood cultures for each
patient and suggestive echocardiographic signs
(mostly transthoracic, app. 20% transesophagian). Clinical signs were also patognomonic
for IE. In 33 cases left side heart was implicated (mostly Staph. aureus, Streptococci including Enterococci) and in only 9 cases right
side of the heart (mostly BGN, fungi, intravenous drug users) as follows:
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mitral lesion 17 cases (40.5%)

aortic lesion 11 cases (26.2%)
double lesion mitro-aortic 5 cases (11.9%)
tricuspidian 7 cases (16.6%)
pulmonary valve 1 case (2.3%)
tricuspidian + pulmonary 1 case (2.3%)
Most of the deaths occurred during the first
2 weeks after apparition of clinical signs (about
70%), while patients followed medical treatment (antibiotic + anticoagulant). Complications in this period are lifethreatening and are
related to a higher mortality rate. In only 7
patients death occurred after imperative surgical treatment due to major complications or
impossibility to sterilize endocardic thrombus
through antibiotherapy. Necroptic examination
of targeted organs during complications of the
IE showed as follow:
myocardial infarction (10 cases = 23.8%)
pericarditis (3 cases = 7.14%)
rupture of papillary muscles (3 cases =
7.14%)
rupture chordae tendinae (4 cases = 9.5%)
- myocardial abscess (2 cases = 4.75%)
intraventricular abscess (1 case = 2.38%)
Extracardial - cerebral embolization (11 cases = 26.2%)
splenic abscess (3 cases = 7.14%)
pulmonary embolia (7 cases = 16.6%)
mesenteric infarct (2 cases = 4.75%)
Global congestive heart failure was found in
almost all the patients, with various degrees of
classification according to NYHA. In 8 cases
there was clear evidence of multiple organ embolization (most frequently brain and pulmonary), as this complication seems to be the
most implicated in the death of these patients,
especially the young ones (under 45 years old).
In few cases, necroptic examination pointed
out hepatic, pancreatic and articulary modifications, with no lifethreatening effect. Microscopical examination of the tissues prelevated
from different affected organs confirmed most
of the macroscopic disorders observed during
necropsy, so immediate cause of the death is
usually easy to establish, even before laboratory
results confirm tissue lesions. Associated illnesses
of the patients were not implicated directly as
main cause of the death. (fig. 1, fig. 2)
DISCUSSIONS
The 42 deaths among patients with IE are
part of the 151 deaths occurred in a large co-

Major Complications in Infective Endocarditis Anatomopathologic Aspects of Targeted Organs

Fig. 1. Cord material necroptic

Fig. 2. Cord material necroptic

hort (868 cases) during 14 years, with no

previous known heart diseases; as it can be
observe, mortality rate in this group is greater
(almost double) compared to patients with different former complaints of heart and circulatory system. Necroptic data obtained showed
that, however, almost half of them (especially
over 40 years old) had infraclinical tissue modifications, especially myocardial and atherosclerotic. Its clear that are many persons theoretically healthy, with no clinical signs or symptoms which may develop severe complicated
forms of IE in direct connection with different
tissular lesions of the hart. This fact can lead
us to a more appropriate conclusion, that mortality is finally higher in patient with previous

modification of the targeted organs or suffering of various associated illnesses. The medium age of the studied group was a little bit
over 50 years old, lower than the European
mean, which is situated over 55 years old (8).
General mortality of the cohort (224 death/868
patients=25.8%) is even higher compared to
most of European countries in which varies
from 9 to 19% (9). This criteria situate Romania
to the intersection between occidental model of
IE (with mortality rates around 15%) and the
austere model, in which mortality reach 40-50%. Another characteristic of the studied
group is represented by the high percent of
subacute IE (app. 10% of the deaths), 3-4 times
higher than data in occidental model (10). Fatal
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M.E. Hurmuzache

evolution in subacute IE often occurs in young

patients with neglected affections (throat, endocardial, articulary, nephretic), that denotes
a still lower surveillance of the medical system
in youth. Fortunately, even if this indicator is
at high level, there are only few cases of IE in
intravenous drug users, as this region is little
touched by this scourge. Microbiological agent
incriminated, isolated from blood cultures, respect the actual published data (11) with a growing prevalence of Staph. aureus and Enterococci (!cateterism sometimes even unnecessary) but still with a high prevalence for Streptococci A,C,G, somehow characteristic for the
Balkans. For sure, future will show us a growing rate of IE with fungi, as there are more and
more immunocompromised hosts (age, associate diseases, AIDS, intravenous drug users,
excess of antibiotherapy). Data from clinical
examination, imagistic investigation, followed
by necroptic macroscopy/microscopy showed
that left side IE is much more severe than right
side attaint and leads to more frequent complications (especially embolization and infarcts)
and death. Another interesting thing to remark
is the higher prevalence of mitral lesions (40%)
than data from literature (app. 25%) (5,6) and
myocardial infarction (26% vs. 12-14% in literature). As the endocardial lesion and thrombus are growing in dimension, the risk for
embolization, infarction and subit death be-

come higher. It is also very clear that early

diagnosis of IE and its complications, related
to high performance investigations (imagistic, laboratory) associated to a appropriate antibiotherapy and, where needed, surgical intervention, can lead to a lower degree
of mortality.
CONCLUSIONS
Data obtained from 42 patients with fatal IE
showed there are some characteristics related
to our region and country, as follows:
Lower age of death
Still higher rate of fatal subacute IE
Low rate diagnosis in previous heart disfunctions
Higher general mortality in IE than reported
in occidental model
Higher prevalence of mitral localization and
myocardial infarction growing quota for
Staph. aureus and Enterococci, but still high
rate for Streptococci A,C,G.
Still low rate of cardiac surgery in complicated forms.
The existence of a correlation between localization of the injury, complications, etiological agent, age, associated diseases and the
fatal evolution of the diseases is anyway very
clear, so all data obtained, intravitam or necroptic, should be useful for a better monitoring of this severe illness.

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