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| Streptococcus viridans bacteria. PHIL |
Definitions and Overview
Infective
Endocarditis (IE) refers to infection that forms on the heart valves or
inner lining (endocardium) of the heart, usually as a result of
bacteria entering and circulating in the bloodstream. As the
consequences can be severe if left untreated, prompt and accurate
diagnosis of IE is critical. The complications may include heart
failure, kidney failure, stroke, or death. Even with appropriate and
timely treatment, a small percentage of patients will experience
complications and require surgery to replace or repair the infected
heart valve.
A variety of bacteria and other infections can cause endocarditis including most commonly staphylococcus aureus (“staph”) and streptococcus viridans.
The streptococcus (“strep”) that causes endocarditis is related to, but
different from the strep that causes sore throats. This distinction is
important because rheumatic heart disease can occur after strep throat
(due to Group A streptococcus), and rheumatic heart disease can then
increase the likelihood of other infections (see below). Less commonly
other organisms, like some forms of fungus, can cause endocarditis
whereas viruses do not. When these bacteria get into the bloodstream,
they may settle on the heart valves and start to grow, attracting white
blood cells that fight off infection. This process also stimulates very
small blood clots, called thrombi, to form on the valve. The combination
of bacteria, white blood cells, and thrombi form masses that are called
vegetations which vary in size but can grow as large as several
centimeters. If these vegetations dislodge from the valve, they may
travel via the bloodstream to other areas of body (embolization),
including the brain in some cases, which can cause a stroke.
Understanding causes and conditions that predispose to endocarditis is
important as IE can be associated with significant debilitation and
mortality, particularly if the diagnosis is unrecognized or delayed.
Often,
endocarditis is classified as left-sided or right-sided, referring to
the side of the heart in which it occurs. Endocarditis is most common on
the aortic and mitral valves, which are on the left side of the heart.
Right-sided endocarditis almost always affects the tricuspid valve,
situated between the right atrium and right ventricle, and only rarely
the pulmonary valve. This distinction is important because left sided
endocarditis is associated with more serious complications and generally
requires a longer course of treatment.
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| Vegetation on tricuspid valve by echocardiography. Arrow denotes the vegetation. |
How common is endocarditis and who gets it?
The
incidence of IE was relatively stable between the 1950s to early 1980s
affecting around 4 per 100,000 patient-years. This means that if you
followed 10,000 patients for 10 years, there would be 4 cases of
endocarditis. In the mid-1980s, the incidence increased to approximately
6-12 per 100,000 patient-years, and this rise was thought to be related
to increase in intravenous use of illegal drugs like heroin (See below
Predisposing Conditions). Endocarditis is 3 to 9 times more common among
men. Additionally, the average age of patients with endocarditis has
increased over the past 30 years. A number of predisposing conditions
increase an individual’s risk for developing endocarditis; however, in
some studies predisposing conditions were not identified in at least a
quarter of patients.
What predisposes a patient to get endocarditis?
Certain conditions increase a person’s risk for contracting endocarditis. These will be discussed individually.
Intravenous Use of Illegal Drugs: The
risk of IE is much higher among patients who use injection drugs
compared with the general population. This risk is related to the
introduction of high amounts of bacteria into the bloodstream with drug
injection because of contaminated drug solution or dirty needles or
syringes. One study evaluated 1150 intravenous drug users who were
hospitalized over 12 months, and IE was diagnosed in 75% of these
patients (Matthew, 1995). Endocarditis must be seriously considered in
any patient with a history of intravenous drug use who presents to a
hospital with a fever.
Rheumatic Heart Disease: Rheumatic fever is a delayed result of a throat infection with an organism called Group A streptococcus. Rheumatic heart disease refers to disease of the heart valves that occurs over time after affliction with rheumatic fever. Rheumatic Heart Disease (RHD) is more common in underdeveloped countries, and less commonly seen in people born in the United States. Having said this, RHD is one of the most common causes of valvular abnormalities worldwide.
Degenerative Disease of Heart Valves: Abnormalities that occur over many years as a result of the breakdown of valve tissue are more common among elderly people and are included in this category. These areas of abnormal valve tissue can serve as the nidus, a central point, for bacteria to settle, because the bacteria can stick and set up housekeeping on roughened tissue with irregular surfaces more easily than on the normal smooth-surfaced heart valve. Degenerative mitral valve disease and aortic stenosis (narrowing of the aortic valve) are examples of common degenerative valve diseases associated with higher risk for endocarditis.
Mitral Valve Prolapse: Mitral
valve prolapse refers to degenerative abnormality of the mitral valve
(the valve located between the left atrium and left ventricle), where
the valve tissue demonstrates abnormal motion, or prolapse, during
contraction of the ventricle. Patients with mitral valve prolapse who
also have thickened valve leaflets and leakiness (or regurgitation)
associated with the mitral valve are at higher risk for endocarditis.
The risk of IE in this population is about 5 to 8 times higher than in
the general population (Clemens, 1982).
Congenital Heart Disease: People
who are born with structural abnormalities of the heart, also known as
congenital heart disease, are at higher risk of endocarditis. Congenital
heart disease accounts for about 10-20% of cases of IE. The most common
congenital abnormalities predisposing to IE include bicuspid aortic
valves (aortic valves with two rather than three leaflets, affecting
approximately 1-2% of the general population), patent ductus arteriosus
(congenital communication between the pulmonary artery and aorta),
ventricular septal defects (defect in the heart muscle tissue between
the right and left ventricle), coarctation of the aorta (congenital
narrowing of the aorta), and Tetralogy of Fallot (congenital heart
abnormality consisting of ventricular septal defect, abnormal aortic
root location, narrowing of the outlet of the right ventricle, and
thickening of the right ventricular muscle tissue). Additionally,
patients who have undergone complex surgical correction of their
congenital heart abnormality are among the highest risk category for
complications associated with endocarditis and should be considered for
protective treatment with antibiotics, called prophylaxis, when having
surgical or dental procedures (see Prevention and Antibiotic Prophylaxis
section below).
Prosthetic Valve Endocarditis: Any
form of prosthetic material within the heart can serve as a nidus for
infection and IE. Patients who have had their heart valves either
surgically repaired or replaced with a prosthetic valve are at high risk
of IE. The risk of developing IE of a prosthetic heart valve is highest
in the first year after surgical replacement, and the risk remains
approximately 1% per year thereafter. Because complications associated
with IE of prosthetic valves can be very serious, patients with
prosthetics valves should take preventive antibiotics around the time of
surgical procedures and dental work to minimize the risk of
endocarditis (see Prevention and Antibiotic Prophylaxis section below).
Human Immunodeficiency Virus: Some studies have suggested that infection with the human immunodeficiency virus may be an independent risk factor for the development of endocarditis.
Health-Care
associated endocarditis: Health-care associated IE, otherwise known as
nosocomial endocarditis, occurs mostly in the presence of long-term
intravenous devices placed for medical purposes. For example, patients
who have intravenous lines placed within major central veins (internal
jugular veins, subclavian veins, and femoral veins) and patients with
dialysis catheters are at risk for bacterial spread through the
bloodstream to the heart valves if these lines must stay in place for
several days. These lines may serve as a stopping ground for bacteria to
settle then circulate in the bloodstream. Valvular vegetations that
then form target abnormal cardiac valve tissue, transvenous pacing
wires, defibrillators, and prosthetic valves. Patients who have
indwelling intravenous lines for nutrition (total parenteral [by means
other than the gastrointestinal tract] nutrition) are at higher risk for
more dangerous types of endocarditis, particularly fungal endocarditis.
Prior History of Endocarditis: Patients with a prior history of IE are at increased risk for recurrent IE. After a patient recovers from IE, the heart valves typically are somewhat damaged, and these damaged areas of valve tissue are at much higher risk for recurrent vegetation formation when bacteria is traveling in the bloodstream. These patients are also recommended to take prophylactic antiobiotics around the time of surgical or dental procedures.
Where do the bacteria come from and how do bacteria get into the bloodstream?
Bacteria
are everywhere in our environment and unfortunately cannot be avoided.
However, bacteria do not normally circulate in the bloodstream, and when
significant amounts of bacteria are introduced into the bloodstream,
the body’s immune system must work to fight and destroy them. Tooth
brushing normally causes small quantities of bacteria from the mouth to
be introduced into the bloodstream each day. In people with normally
functioning immune systems these bacteria are quickly destroyed by our
body’s bacteria fighting cells, and are killed before they have time to
settle on the heart valves to develop infection. With prolonged dental
procedures, more bacteria can be released into the bloodstream
increasing the risk of infection of the heart valves. This risk of
infection is highest if there is prosthetic material or abnormal valve
tissue for the bacteria to settle on.
Bacteria
can also be introduced from the ambient air into the bloodstream
anytime the skin is broken and a needle is introduced into the veins,
such as with illegal injection drug use. Large quantities of bacteria
from the skin can then travel with the needle into the bloodstream and
cause bloodstream infection and endocarditis. Rarely, bacteria could be
introduced into the blood with surgical procedures where the bacteria
travel from the skin into the bloodstream through an incision.
Regardless of how the bacteria enter the bloodstream, if the body’s
immune system cannot kill the bacteria, either because there are too
many bacteria or because the immune system is weakened, infection may
occur.
The
onset of this infection can be either acute, referring to development
and progression of severe symptoms over days to several weeks, or
subacute, referring to the development and progression of less severe
symptoms over weeks to months. In most cases of IE associated with
native heart valves, the interval between initial bacteria circulating
in the bloodstream to onset of symptoms is less than 2 weeks in about
80% of patients. Fever is the most common symptom. Fever may be absent
or minimal in elderly patients, patients with severe disability, or
patients with chronic kidney disease. Shaking chills are also noted in
the vast majority of patients. Poor appetite is seen in approximately
25-50% of patients, and weight loss and malaise in 25-35% of patients
with IE. Other symptoms that may be observed include shortness of
breath, cough, stroke symptoms, headaches, nausea or vomiting, muscle or
joint aches, abdominal pain, back pain, and confusion.
What will my doctor find on physical examination?
A
physical examination by a physician is very important if IE is
suspected. Heart murmurs are noted by physicians in 80-85% of patients.
Neurologic abnormalities can be seen in 30-40%. Other findings include
an enlarged spleen and abnormal eye exams. Two types of abnormal
discrete spots on the fingers or toes may also be seen as a result of
embolic phenomena. Small painful lumps called “Osler’s nodes” may occur
on the pulp of the finger tips. “Janeway” lesions are flat, non-painful
areas of discolorations on the palms and soles. Splinter-like
discoloration in the nail beds, called splinter hemorrhages, may be
seen.
How is the diagnosis confirmed?
The
diagnosis of endocarditis is suspected in patients with fever who
present with one or more of the following features: predisposing
condition as discussed above, evidence of bacteria within the
bloodstream as confirmed by blood cultures, evidence on heart
ultrasound (echocardiogram) consistent with the diagnosis of
endocarditis, such as presence of vegetations, or evidence on physical
exam or on radiologic imaging suggesting a vegetation may have traveled
to other parts of the body (embolic phenomena).
Key to the diagnosis of endocarditis, blood cultures are samples of blood, usually drawn from the arm after carefully cleaning the skin, which are sent for culture of bacteria. Usually, at least two samples are drawn 15 minutes apart. The laboratory keeps samples for at least a week because some bacteria take a long time to grow.
Other
diagnostic tests may be helpful, such as chest X-rays to look for
evidence of heart failure due to the endocarditis or to see if the
infection has spread to the lungs due to endocarditis (called septic
pulmonary emboli). Electrocardiograms (EKGs) can be helpful if the
patient has developed any electrical abnormalities due to the infection.
Occasionally, if the infection is severe and has spread to the
surrounding heart muscle tissue, it could damage the normal electrical
system of the heart and cause heart block (see below Complications
section). These abnormalities can be picked up and monitored on an EKG.
A heart ultrasound or echocardiogram is very important in making the diagnosis of endocarditis, because it allows the physician to directly visualize the valve tissue and observe its motion. A transthoracic echocardiogram (TTE), or ultrasound of the heart done by placing an ultrasound probe on the chest, can often detect vegetations as small as 3mm. It can help determine how much movement is associated with the vegetation and its risk for embolization, and can help determine how much leakiness of the valve has developed due to the IE. A TTE also can assess if the heart muscle has been weakened due to the infection. However, many times the vegetations that cause trouble are smaller than 3mm and are not seen on a TTE. In this case, if the diagnosis is suspected by the physician, a transesophageal echocardiogram (TEE) is performed. A TEE is a type of ultrasound performed by placing a thin probe down the throat (or esophagus) and visualizing the heart from the inside. The images generated from a TEE are superior to that of a TTE most times, and a TEE can detect even the smallest of vegetations. A TEE can also help to better characterize the size and location of vegetations, and help determine if the infection is spreading to the heart muscle or abscess.
Guidelines for diagnosis called the Modified Duke Criteria
have been established to help physicians determine how likely
endocarditis may be in a particular patient. Major criteria include
positive blood cultures for typical bacteria that cause endocarditis,
vegetations seen on TTE or TEE, or new valve regurgitation (leak). The
minor criteria include having a heart condition predisposing to
endocarditis, fever (temperature >100.4F or >38C), abnormalities
of the fingers or toes as described above, or positive blood cultures
not quite meeting major criteria. If a patient has one major and one
minor criteria or three minor criteria, the diagnosis of endocarditis is
possible.
Finally,
because patients with prosthetic heart valves are at high risk of
endocarditis, the presence of new fever or evidence of abnormal function
of that prosthetic valve should always raise concern for IE.
How do we treat endocarditis?
Once
the diagnosis of endocarditis is suspected, multiple blood samples
should be obtained prior to beginning antibiotic therapy, and these
blood samples should be sent to the laboratory for evaluation and
culture. People known to be at risk of endocarditis who have fevers for
more than 2-3 days should generally have blood cultures sent to the
laboratory, before starting even oral antibiotics. Even low doses of
commonly used antibiotics such as amoxicillin and azithromycin, can
prevent the bacteria from growing in culture but cannot cure
endocarditis. Then the choice of antibiotic to effectively cure the
endocarditis is hampered. While the blood cultures are being evaluated,
antibiotics should be chosen that cover a broad range of possible
organisms that can cause IE. Once the specific organism is identified by
the laboratory, the antibiotic choice can be simplified to best target
and get rid of the organism.
Antibiotic
therapy for endocarditis should not only eliminate the infection, but
also should do so while causing little or no side effects to the
patient. This is particularly important since the treatment is very
long—usually 4-6 weeks. Identifying the correct organism is crucial in
choosing the right antibiotic. Common antibiotics used to treat
endocarditis include nafcillin or ampicillin, vancomycin, ceftriaxone,
gentamycin, or rifampin. Each of these medicines kill different
bacteria. Because the infection is so severe with potentially
devastating complications, often more than one antibiotic is used to
cure the infection. Unfortunately, some forms of endocarditis may not
result in blood cultures that grow a specific organism (culture-negative
endocarditis), and antibiotic therapy must be chosen empirically.
Typically, antibiotics are initially given intravenously to suppress the
circulating infection within the bloodstream. Depending on the type of
organism and severity of infection, antibiotic therapy may be changed to
oral therapy when the infection is under control without evidence of
severe complications. Antibiotics are continued for anywhere from 4-6
weeks if blood cultures show no further organism growth, or longer if
blood cultures continue to show bacterial growth. In many cases, after a
brief stay in the hospital to monitor for complications, the patient is
sent home with a long-term intravenous line to continue to receive
antibiotics at home. Infection in these catheters is uncommon since
antibiotics are being given, unlike the catheters used for dialysis.
What are the complications associated with endocarditis?
1.) Abnormal valve function: The
bacteria can literally eat away at the valve, destroying valve tissue
and causing the valve to leak (regurgitation). Less commonly, large
vegetations can interfere with the opening and closing of the valve.
Patients with evidence of abnormal valve function, as a result of
destruction or large vegetations, may develop heart failure and are at
very high risk for death due to IE. This heart failure occurs because
the leaking valve puts great stress on the heart muscle as it tries to
compensate for the infection. Regurgitation of the aortic valve (valve
between the left ventricle and aorta) is associated with more severe
heart muscle dysfunction, than regurgitation of the mitral valve and
patients with aortic valve IE more commonly need to be referred for
surgery. However, severe mitral valve regurgitation can also result in
severe heart failure that ultimately will require surgery.
2.) Unstable Prosthetic Valves:
Infection on prosthetic tissue is very difficult to cure with
intravenous antibiotics, and removal of the infected valve with
placement of a new valve often must be considered. Additionally,
infection associated with prosthetic valves can spread to heart muscle
tissue surrounding the valve and form an abscess (a contained infection)
in the heart tissue surrounding the valve. This can result in weakening
of this tissue that holds the valve in place. Sutures may give way
leading to an unstable prosthesis, called dehiscence. Intravenous
antibiotic therapy is ineffective in this situation, and surgical
intervention is necessary to prevent serious complications or death.
3) Abscess: While
more common with prosthetic valves, abscess forming around the valves
can also be seen with endocarditis of the heart’s own valves. These are
very hard to cure with antibiotics since they are typically walled off
and the antibiotics can’t penetrate to kill the bacteria. Often,
patients with abscesses must be considered for surgery to replace or
repair the valve.
4) Heart block: Bacteria,
usually in association with an abscess, also may destroy part of the
heart’s electrical system, called the conduction system, causing blocks
or “shorting” of the signals that activate each heart beat. Ultimately
this can lead to slow heart rhythms called heart block. For this reason
it is very important that all patients have an electrocardiogram (EKG),
which can detect early signs of heart block.
5) Emboli: As
previously mentioned, small parts of the vegetation can break off the
heart valves and travel into the circulation. If the vegetation is on
the left side of the heart (aortic or mitral valve), the most common
site for them to lodge causing a stroke; they can also travel to the
kidney and spleen, but these are often not suspected on physical
examination. Rarely, an embolus to the coronary artery can cause a heart
attack. When the infection is on the right side of the heart, the
emboli can travel to the lungs where they can cause small areas of
pneumonia. These are called “septic pulmonary emboli” and have a
distinct appearance on the chest X-ray. When antibiotics are effective,
they usually prevent further emboli. When emboli continue to occur after
patients have received antibiotics for more than a week, it raises
concern that the antibiotics are ineffective in curing the endocarditis.
6.) Uncontrolled Infection Despite Medical Therapy: Patients
who have persistent infection despite several weeks of appropriate
antibiotic therapy in the form of ongoing fevers, further emboli, the
development of an abscess or blood cultures that continue to grow the
bacteria. This is termed a failure of antibiotic therapy. For patients
who fail antibiotic therapy, surgery may be needed to eradicate the
infection and preserve functioning of the heart valve.
When
antibiotics do not eradicate the infection, surgery may be needed.
Complications associated with IE that place patients at high risk for
severe health consequences or death typically require surgical repair or
replacement of the heart valves. Surgical intervention typically refers
to open heart surgery requiring an incision through the sternum
(midline bone in the chest supporting the ribs) to access the disease
valve for either repair of the damaged valve or replacement with a
prosthetic valve. While there was initially concern that the new valve
would become infected, it turns out that as long as antibiotics are
being given at the time of the surgery and continued well after surgery,
infection of the new valve is uncommon.
Can endocarditis be prevented and how?: Endocarditis Prophylaxis
In
the 1950s physicians first theorized that antibiotics could be given
before medical or dental procedures to prevent endocarditis as these
procedures are commonly associated with bacteremia, defined as bacteria
within the bloodstream. The American Heart Association first published
guidelines in 1955 specifying that when patients predisposed to
endocarditis should take antibiotics such as before dental work. While
the guidelines have been modified over the years, these guidelines were
radically changed for the first time in 2007 based on several of the
following principles: 1) endocarditis usually occurs when bacteria enter
the bloodstream in the course of everyday life rather than during
procedures; 2) antibiotics given at the time of the procedure likely
prevent only a small number of cases; 3) risk of reactions to
antibiotics may be greater than the benefit derived; and 4) good oral
health and dental hygiene are probably much more important than giving
antibiotics at the time of dental cleaning. Additionally, the risk of
overuse of antibiotics leads to development of antibiotic resistance and
future difficulty in treating infections—so overuse of antibiotics
should be avoided. Endocarditis prophylaxis with antibiotics is now
recommended only for patients who are at the highest risk of significant
debilitation or death if IE is acquired. Moreover, antibiotic
prophylaxis was not recommended based solely on an increased lifetime
risk of acquisition of IE. These guidelines recommend that “infective endocarditis prophylaxis for dental procedures is reasonable only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis.”
Cardiac
conditions associated with the highest risk of adverse outcomes from
endocarditis for which antibiotic prevention with dental procedures is
reasonable include the following:
1.) prosthetic heart valves or prosthetic material used for heart valve repair
2.) previous history of IE
3.) complex
congenital heart disease (unrepaired congenital heart abnormalities
that result in low oxygen level, and patients with prosthetic material
placed surgically to correct the congenital abnormality)
4.) heart transplant recipients who develop dysfunction of their valves due to IE
For
patients who have valve abnormalities not classified as the highest
risk, but more moderate risk for developing endocarditis, such as
patient with mitral valve prolapse, the decision regarding use of
antibiotic prophylaxis should be individualized by physicians according
to the risk of severe disability or death associated with IE for that
particular patient.
Conclusions
Endocarditis
refers to infection associated with heart valves and is typically
treated with either antibiotic treatment or surgical valve repair or
replacement. It is important to understand the predisposing conditions,
signs, and symptoms of endocarditis because early identification and
treatment can help to prevent serious complications such as valve
dysfunction, heart failure, kidney failure, stroke, and death.
Links
Search under patient information for endocarditis on the following internet sites:
www.nhlbi.nih.gov
www. jama.ama-assn.org
www.uptodate.com
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