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Infective
Endocarditis:
A Disease Not
To Be Missed
1
Infective Endocarditis: a Disease Not To Be Missed
Ann Krinks, RGN, BA (Hons), Trainee Advanced Nurse Practitioner (MSc Advanced Practice)
Infective endocarditis is a serious disease of the heart; despite this cardiac infections such as
endocarditis are viewed as the Cinderella of cardiac diseases often falling into a place of
secondary importance with conditions such as Acute Coronary Syndrome (ACS) enjoying most
clinical attention. The presentation of infective endocarditis is diverse and the condition can
masquerade as many other illnesses causing the patients to present to essentially any clinical
specialities.
While tremendous successes have been made in the detection and management of ACS the
same cannot be said for infective endocarditis. Indeed, for infective endocarditis mortality
remains high with more than a third of patients dying within the first year after diagnosis.
Despite advances in the diagnostic and therapeutic strategies, the fatality rate of the disease
has not decreased in the last 30 years. Coupled with this the fundamental nature of infective
endocarditis is changing and new epidemiological genesis is emerging driven primarily by
advances in medical therapies.
Like with many conditions early identification of patient’s with infective endocarditis is crucial to
survival but the complexities of the pathophysiology of the disease coupled with a lack of
awareness of the condition means that the diagnosis is all too often delayed. It is essential then
to promote awareness of infective endocarditis in order that clinicians can recognise signs and
symptoms and know how to respond.
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Epidemiology
Infective endocarditis is a deadly disease with a high mortality rate; over 30%
of patients will die within the first year of diagnosis (Thuny et al. 2012). Despite
the evolution in antibiotic therapy and sepsis prevention, the incidence of
infective endocarditis has not declined in the last 30 years (European Society
Cardiology Guidelines 2009). Infective endocarditis is a microbial infection of
the endothelial surface of the heart and heart valves with serious even fatal
consequences. It occurs when bacteria enter the bloodstream and attach to a
damaged portion of the endocardium, the inner lining of the heart or heart
valves where they multiply and form vegetation. This vegetation can break off
and cause emboli to occlude blood vessels within the body. If the vegetation
breaks off from the right side of the heart emboli can travel to the pulmonary
circulation and cause Pulmonary Embolism and lung abscess formation. If the
vegetation breaks away from the left side of the heart, the emboli can travel to
the brain causing stroke, to the kidneys, spleen or coronary arteries resulting in
infarction. The causative organisms are mainly bacteria and fungi, of which
staphylococcus aureus, staphylococcus epidermis, streptococcus viridians,
enterococci and candida albicans are most commonly associated with this
infection (Carmela et. al 2012).
Historically endocarditis was 100 percent fatal and was associated with heart
valve damage from rheumatic heart disease, now uncommon in westernised
counties (Prendergast, 2006). The pioneering work of the 19th century
physician William Osler, identified that endocarditis was a disease to be
suspected in all cases of fever with heart murmur along with this his discovery
of the painful erythematous nodes on patient’s hands and feet now known as
Oslers nodes made him an eponym of the disease today. (Grinberg & Solimene
2011).
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Since Olslers first description the fundamental nature of the disease has
changed as has its target recipients. The emergence of new constellation of at
risk groups include:
 Those with pre-existing heart defects and degenerative heart disease
( Thanavaro & Nixon 2014)
 People who inject drugs and risky social behaviour such as body
piercing and tattoos (Furat et al. 2014)
 Recipients of prosthetic valves (Rekik et al. 2010)
 People with long term indwelling catheters or implanted devices
(Baddour et al. 2015)
 Immunocompromised patients & previous endocarditis
The increasing ageing population reflects a large ‘at risk’ group of patients
susceptible to endocarditis from degenerative heart disease with more than
50% of all cases of endocarditis seen in over 60’s age group (Tornos et al.
2011).
Nosocomial related infective endocarditis is emerging as a growing health
concern due to increasing numbers of invasive procedures carried out in 21st
century health care, with mortality within this group more than 50%
(Fitzsimmons et al. 2010). Intravascular devices such as cardiac pacemakers,
internal defibrillators as well as long term indwelling vascular catheters can
predispose patients to developing infective endocarditis (Cunha 2011).
Microorganisms originating from the skin (staphylococci) and urinary tract
(enterococci) being the most common pathogenic cause account of up to 80%
of all cases of infective endocarditis ( Moreillon 2010). It has been suggested
that patients with infective endocarditis have an in hospital mortality rate as
high as 26%, of which could be higher as deaths occurring after discharge have
not been recorded. (Fedeli et al. 2011)
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Almost any type of structural heart disease can predispose to infective
endocarditis especially valveular heart disease. Infective endocarditis usually
affects damaged valves in the left side of the heart, mitral valve prolapse and
degenerative mitral and aortic regurgitation. Prosthetic valve endocarditis can
be seen early onset within 60 days of surgery, caused by perioperative valve
contamination with staphylococci or late onset due to native valve infection
usually due to streptococci (Ashley &Niebauer 2004). Other predisposing
conditions include hypertrophic cardiomyopathy, sub aortic stenosis and
ventricular aneurysm as well as congenital defects such as coarctation of the
aorta, ventricular septal defect and bicuspid aortic valve.
Infective endocarditis in intravenous drug users is a fast growing problem due
to increasing drug misuse. This group of patients tend not to have any preexisting cardiac disease and affects the right heart valves, their presentation
also differs from classic infective endocarditis presenting with pneumonia or
septic pulmonary emboli ( Furat et al. 2014)
Infective endocarditis has existed for over 450 years; new trends in
epidemiology related to changes in social behaviour have made it an emerging
problem. A number of factors would account for the change in epidemiological
characteristics of infective endocarditis, alongside this with increasing life
expectancy and medical advances, the incidence of degenerative heart disease
and implanted devices is increasing and as such, it is likely that there will be a
rise in the incidence of infective endocarditis in the future. In the postantibiotic era, that now challenges health care providers, many infections are
now caused by antibiotic resistant bacteria, which make the management of
infective endocarditis even more challenging (Beynon et.al 2006).
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Presentation
Considered a ‘disease in disguise’ infective endocarditis can manifest with
varied clinical presentations ranging from non-specific viral symptoms to
catastrophic events such as embolic stoke and myocardial Infarction. Many
patients may initially experience only general malaise, low grade fever and
viral illness type symptoms making diagnosis difficult, some 25% of patients
take over a month to be admitted to hospital after onset of their initial
symptoms (Connaughton & Rivett 2010).
A variety of dermatological signs may be seen, as a result of small emboli
travelling to peripheral vessels, however this can be a late sign indicating that
the disease has become established (Figure 1). Valve destruction from infective
endocarditis will cause murmurs to develop and subsequently may lead to
reduced cardiac output and heart failure, heart failure is the most common
complication of infective endocarditis. Retinal haemorrhages may be seen on
fundoscopy and petechial rashes on the body , inside eye lids and on oral
mucosa may be seen as the result of travelled emboli. Anaemia and clinical
signs of infection including raised inflammatory markers are common
pathology findings.
Patients can present to a variety of specialities who are likely to consider their
own speciality diagnosis first. Infective endocarditis can present with
explainable symptoms which fit with speciality diagnosis such as stroke,
abscess formation or renal failure, which may however be a symptom of
infective endocarditis and result in an incorrect diagnosis, common examples
being malignancy, tuberculosis or other chronic disease.
It has been suggested that the most important tool for recognising infective
endocarditis is “suspicion”. Initial thorough clinical examination of patients is
essential; a heart murmur with fever should alert suspicion to the presence of
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infective endocarditis, 48% of patients have been found to initially present
with a new heart murmur and 20% with a worsening known heart murmur.
(Hoen & Duval 2013).
The diagnosis of endocarditis is based on blood culture and echocardiographic
findings. However, recognition of high risk patients combined with thorough
clinical examination is paramount as microbiological findings and imaging
studies are not always initially available at the onset of care.
Figure.1 Dermatological signs of infective endocarditis
Nail fold infarcts from systemic
emboli
Splinter haemorrhage – thin linear
line haemorrhage under the nail bed
Oslers nodes- small tender red to
purple nodules on the pulp of distal
digits of fingers and toes
Janeway leisons-small painless
macular lesions on palms and soles of
feet
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Defining and Exploring the Problem
Significant advances in diagnostics and treatment for Coronary Heart disease
within the last decade has resulted in improved survival rates and reduction in
morbidity. Research and medical advances within cardiology have mainly
focused around Acute Coronary Syndrome (ACS) with advances in early
revascularisation strategies and secondary prevention given precedence
(Bhatnager et al. 2015). Unfortunately, the tremendous advances made in ACS
management have not mirrored cardiac infection, as its fatality rate has not
decreased.
The incidence of infective endocarditis is difficult to determine due to the
variation in succession of the disease. The global burden of the disease is
largely unknown and unlike other infectious diseases does not require
mandatory reporting to public health agencies, as such a true picture of its
epidemiology is not evident (Baddour et al.2015). Analytical data is often based
on definitive cases of infective endocarditis therefore reflecting in a misleading
relatively low incidence (Fowler et al.2004). However evidence suggests that if
deaths from embolic complications of the disease where reported as infective
endocarditis as the initial diagnosis, the mortality rate would be considerably
higher (Durante-Mangoni & Utili 2014). Indeed, neurological and cardiac
symptoms may precede a diagnosis of infective endocarditis and documented
as such before the possibility of cardiac infection is considered. Studies have
shown an increasing incidence of infective endocarditis over the last decade
despite a substantial decrease in the prevalence of rheumatic heart disease as
a predisposing factor (Sayan & Carter 2013). This calls to question that
infective endocarditis is under diagnosed and is often masked by other
conditions.
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Several factors would suggest reasons for this under diagnosis. Studies have
shown that Infective endocarditis is difficult to interpret and is often preceded
by other diagnosis. Cerebral complications are the most severe extra cardiac
complications of infective endocarditis, with up to 42% of patients
experiencing cerebral emboli (Epaulard et al. 2009). Ischemic and
haemorrhagic stroke precede the diagnosis of infective endocarditis in 60% of
patients (Hoen et al. 2013). In contrast, however evidence from a USA study
into the readmission for infective endocarditis after stroke was found to be
negligible disbanding the above evidence, however this study was based on
patients without clinical evidence of Infective endocarditis (Chu et al. 2015).
Clinicians must consider infective endocarditis as a possible underlying
diagnosis when confronted with a patient with stroke, perform
echocardiography, and blood culture even if fever is lacking as it has been
established that the risk of stroke falls rapidly after the initiation of effective
antimicrobial therapy (Derex et al. 2009).
Similarly, infective endocarditis can result in coronary artery emboli and
present as acute myocardial infarction and conduction disorders mainly AV
blocks, secondary due to atrial septal abscess formation (Brown et al .2015).
Cardiac complications are commonplace in patients with infective endocarditis
of which heart failure is recognised as the most frequent cause of death
(Paterick et al. 2007). According to figures from the National Heart Failure
Audit (2013), around 44,000 patients are admitted to hospital per year with
heart failure. Considering these facts, it is questionable that a considerable
amount of these patients may have an underlying infective endocarditis as
their primary diagnosis. The initial cause of these findings may be overlooked
especially given the time constraints of interventions such as thrombolysis in
acute stroke and angioplasty during acute Myocardial Infarction (MI). Clinicians
need to be aware of alternative causes of acute (MI) other than atherosclerotic
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plaque rupture, especially in the absence of coronary heart disease risk factors.
The suspicion of acute MI secondary to septic vegetation embolism must be
considered in patients with prosthetic valves, as current strategies for
treatment of acute MI such as percutaneous intervention or thrombolysis is
highly dangerous in this instance (Luther et al. 2011).
Furthermore other less obvious presentations have been reported with
infective endocarditis as the primary cause ; Major vessel emboli due to
infective endocarditis can present with lower limb and back pain and
misdiagnosis can occur in this setting (Chung et al. 2014). Infective
endocarditis often presents initially with pneumonia or septic pulmonary
emboli in intravenous drug users (Furat et al. 2014). Although reported as a
rare presentation retinal artery emboli manifested by sudden complete vision
loss can arise from dislodged emboli secondary to infective endocarditis
(Ziakas et al. (2014). It can be established then that infective endocarditis can
exhibit as a diverse presentation of disease with live threatening outcomes.
Lack of Infectious Endocarditis Ownership
The established clinical presentation of patients with endocarditis is highly
variable with multiple manifestations, resulting in delayed or missed diagnosis.
Quick identification of patients at highest risk of death may offer the
opportunity to change the course of the disease and improve prognosis.
However, given the pressures of today’s NHS especially within emergency care,
much of the emphasis on treating the patients presenting condition takes
precedence over establishing the underlying cause. This calls into question
which speciality and which physician should care for patients with infective
endocarditis? Given the varied presentation of the disease, patients are
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generally treated by an array of medical professionals with different
experience in identifying and treating the condition.
Emergency medical professionals within A&E are at the frontline of patient
care; it is here that the initial ‘suspicion’ of infective endocarditis and the
recognition of ‘at risk’ patients should begin. The initial diagnosis of infective
endocarditis may not be at the forefront of the differential diagnosis for the
junior clinician in A&E. However emergency physicians have an important role
to play in the process of early recognition and to provide education to patients
who are at a high risk of developing infective endocarditis, therefore strategies
to improve management of patients with infective endocarditis are needed.
A recent European study that looked at the management strategies for
patients with endocarditis demonstrated a significant reduction in mortality
when patients are managed by an established multidisciplinary team involving
cardiologist, a specialist in infectious diseases, a microbiologist and a cardiac
surgeon (Chirillo et al. 2013). However, evidence from the hospitalist model of
care in the USA in which patients are under the care of the generalist physician
from admission to discharge has been associated with improved patient
outcomes (Meitzer et al. 2002). Patients with acute medical problems are
generally admitted to medical assessment units via A&E and are under the
care of the acute physician until triaged to a medical speciality, this model may
not benefit certain subgroups of patients particularly those patients whose
illness fails to align with a medical speciality (Fielding et al. 2013)
The European Society of Cardiology guidelines for the management of infective
endocarditis (2015) states that the disease needs a collaborative approach
from the ‘Endocarditis Team’. It suggests that no single practitioner will solely
be able to manage and treat these patients as infective endocarditis is not a
single disease and that a multidisciplinary approach involving expertise from a
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variety of specialists is paramount to positive patient outcome. This
multidisciplinary approach is seen as best practice and has been shown to
reduce one-year mortality by over 50%, however it is not commonplace for
infective endocarditis patients (Chambers et al. 2014).
The presence of the endocarditis team may be evident in large tertiary centre
hospitals with cardiac surgeons to hand however it would appear that this
collaborate approach to patient care is lacking in many smaller district general
hospitals. In such cases, the general physician or cardiologist may care for the
infective endocarditis patient. It is recommended that patients should be
nursed in a specialist area by staff with competences required to recognise
deteriorating valve function and other complications, ideally a Coronary care
unit. However, advances in treatments for acute ST elevation myocardial
Infarction (STEMI) such as primary angioplasty has led to a shift in role of the
coronary care unit. With the majority of acute STEMI patients being treated at
primary PCI centres the demographics of the district general coronary care unit
has changed, from that of acute care setting to more generic general medical
unit comprising of more elderly patients with multiple co-morbidities (Walker
et al. 2012). Critical care trained cardiac nurses are now frequently caring for
lower acuity patients resulting in deskilling and job dissatisfaction of an
experienced workfare as well as compromising patient care and safety (Driscoll
et al.2013). Chambers et al .( 2014) identified difficulties and impracticalities of
setting up infective endocarditis teams in small hospitals and recommends that
there are strong links and established means of communication with the
endocarditis teams at specialist cardiothoracic centres.
In summery it is evident that patients with infective endocarditis need care
from multiple specialities but this can be difficult to implement in small district
hospitals adding to poorer outcomes for this patient group.
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Lack of Awareness
The concept that infective endocarditis is an uncommon disease is one that is
replicated in much of the past literature, this could be likened to severe sepsis
which up until 1991 had no real definition and wasn’t recognised . It was not
until recognition of Systemic inflammatory response syndrome (SIRS) that
awareness campaign groups such as the Surviving Sepsis Campaign and Global
Sepsis Alliance set out to raise awareness and provide guidance in recognition
and management of severe sepsis (McClelland 2014). Currently throughout the
UK, the Survive Sepsis Organisation has produced Sepsis Campaign guidelines
for implementation within NHS Trusts focusing on the aggressive management
of all patients with sepsis in order to ensure they receive optimal care.
The misconception that infective endocarditis is a disease of the past may well
deter the clinician into thinking that it is a condition that will not be
encountered in daily clinical practice. The clinical presentation of patients with
endocarditis is highly variable, often missed or not clinically suspected until
diagnosed at post-mortem; this is evident from post mortem studies, which
showed 38% of cases not diagnosed unit autopsy (Fowler et al. 2004).
Although taught to all medical students as part of their curriculum, studies
have shown a lack of knowledge and need for improved education about
infective endocarditis. A recent study of 136 medical and dental students
identified that only 25% had an acceptable levels of knowledge when
questioned about the causative bacteria and underlining cardiac conditions
that pre dispose patients to endocarditis, despite passing a theoretical course
about endocarditis within a 2 years window ( Zarei et al 2008). A further recent
study in Saudi Arabia replicated similar findings, which highlighted that more
education in this field is required (Fawzan et al. 2014)
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A significant problem in diagnosing infective endocarditis is that diagnosis is
often made too late as initial symptoms such as fever and malaise can be
mistaken for viral illness especially when patients present to their GP. The
significance of this has been questioned in the media (Daily Mail 19 March
2014) reported that of a 42 year old man who died of infective endocarditis
after first visiting his GP with symptoms of night sweats and lethargy, despite
having a pre-existing congenital heart condition he was diagnosed and treated
for a chest infection. After two courses of antibiotics and worsening symptoms
and referral to a hospital consultant blood cultures failed to diagnose
endocarditis (presumed false negative results), due to delays in
echocardiogram the patient suffered a cardiac arrest and subsequently died.
Many patients at risk form endocarditis such as those with congenital heart
defects, prosthetic and degenerative valve disease are unaware of the serious
implications of the disease and the preventative measures they should take for
avoidance (Stucki et al. 2003). Patients should be aware not to take antibiotics
for fever of unclear origin; further more patients in high-risk groups should
inform their GP and insist that blood cultures are taken before being
prescribed antibiotics. The need for good dental hygiene and prophylactic
antibiotic therapy in certain dental procedures is imperative to avoid infection
(Stucki et al. 2003).
Risk-taking behaviours such as tattoos and body piercings have become
common place in today’s society and evidence now suggests an associated risk
of developing infective endocarditis in high risk groups i.e people with valve
problems or congenital heart defects (Junior et al. 2014). Indeed high risk
patients need to be aware of the clinical signs and symptoms of infective
endocarditis and the need to seek early medical help. The need for patient
education is addressed in the National Institute for Health and Clinical
Excellence (NICE) 2008 guideline on the prophylaxis against infective
14
endocarditis in adults and children undergoing interventional procedures . The
guideline recommends that health care professionals teach patients about the
symptoms of infective endocarditis and the risks of non-medical invasive
procedures such as body piercing and tattooing.
The established key points can therefore be summarised;

Understanding the predisposing factors that make a patient susceptible
to infective endocarditis is critical to early recognition, diagnosis and
aggressive treatment.
 Clinicians should be particularly attentive to possible diagnosis of
endocarditis in patients with valve disease who present with fever,
clinical deterioration and embolic events.
 Missed diagnosis is common due to lack of awareness of infective
endocarditis.
 Bias exists against diagnosis of infective endocarditis, as it is perceived to
be an uncommon disease.
 Neurological, cardiac or vascular diagnosis may precede infective
endocarditis diagnosis.
Management
Early recognition and investigation is crucial in identifying infective
endocarditis. Blood cultures should be taken on initial presentation and ideally
before starting antibiotics, to prevent false negative results. Early
echocardiogram is the test of choice although transthoracic echo can have
inadequate views in up to 20% of patients and has a sensitivity of 60%.
Therefore transoesophageal echo is seen as the gold standard test of choice
especially for detecting smaller emboli <5mm, and has a sensitivity of over
15
90%. Serial imaging may be required in patients with initial normal study in
whom diagnostic suspicion persists.
Definitive diagnosis of endocarditis is based on the modified Duke criteria
which combine the clinical, echocardiographic and microbiological findings of a
suspected patient (Li et.al 2000). Although this tool provides high specificity
and moderate sensitivity for the diagnosis of infective endocarditis clinical
judgment is essential at the outset of care . Treatment of infective
endocarditis includes supporting cardiac function, preventing complications
and eradication of infection with lengthy intravenous antibiotics, up to six
weeks duration. Despite antibiotic treatment up to half of patients with
infective endocarditis will require surgery to repair or replace the valve.
Prevention and early diagnosis therefore are the key to reducing morbidity and
mortality from this disease. Vigilance is paramount, it can be said that the
most important tool for recognising infective endocarditis is “suspicion”.
Conclusion
It has been established that infective endocarditis is a serious condition with
often-fatal consequences if not recognised and treated early .Despite rapid
development of advanced diagnostic methods, evolution of antimicrobial
therapy and sepsis prevention infective endocarditis continues to create
significant morbidity and mortality within today’s health care environment.
The incidence of the disease has remained almost unchanged over the past
few decades despite the substantial decline in rheumatic fever in the
developed world. Infective endocarditis remains an illness that is difficult to
diagnose and treat therefore poses a challenge to clinicians.
Medical advances in coronary heart disease made over the last decade have
resulted in improved survival rates for patients with acute coronary syndrome;
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unfortunately, this has not translated into the gains for infective endocarditis,
which appear to have taken a back seat as its fatality has not decreased . The
expansion of the elderly population has given rise to an escalation in
degenerative heart disease, now considered a major predisposing risk factor
for infective endocarditis. An increase in intra cardiac devices, prosthetic valve
replacement, nosocomial infections along with antibiotic resistance have been
identified as key risk factors. It is likely that there will be a rise in the incidence
of the disease in the future as new constellation of at risk groups are identified
such as intravenous drug users and those with body piercings and tattoos.
The clinical manifestations of infective endocarditis are so varied that they may
be encountered in any of the medical specialities. The diverse nature and
evolving epidemiological profile ensures it remains a diagnostic challenge to
clinicians and subsequently often goes undiagnosed. Many cases of infective
endocarditis are missed completely, patients may present with embolic events
because of disease progression which is treated as the primary diagnosis. Lack
of awareness of the disease exists as it is misconceived to be an uncommon
entity in todays healthcare.
Rapid identification of patients at risk of developing endocarditis may offer
the opportunity to change the course of the disease and improve prognosis.
Vigilance is the key to successful recognition of this ‘Cinderella’ of diseases.
The recognition of infective endocarditis is everyone’s concern and building
ownership is a top priority.
It is inconceivable that in the 21st century patients are still dying from a
treatable disease that was prominent in our grandparent’s era. It is time to
unmask the camouflage of infective endocarditis, banish its enigma and raise
its profile in order to save lives in the future.
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