Nonbacterial thrombotic endocarditis

Defined as vegetations on the valve surface, rich in fibrin and platelet aggregates but devoid of
inflammation or infective organisms
Definition / general
 First described by Zeigler in 1888, who called it "thromboendocarditis"
 In 1936, Gross and Friedberg coined the term "nonbacterial thrombotic endocarditis" (NBTE)
 Defined as vegetations on the valve surface, rich in fibrin and platelet aggregates but devoid
of inflammation or infective organisms
Terminology
 Also called marantic endocarditis
Epidemiology
 NBTE is uncommon but underestimated as symptoms are often attributed to other diseases
Sites
 Cardiac valves and endocardial surface
Pathophysiology
 Thrombotic endocarditis develops due to endothelial damage and subsequent exposure of the
subendothelial connective tissue to circulating platelets
 The factors involved in pathogenesis can be divided into initiating NBTE and subsequent
development of vegetation
 Factors implicated in initiation are: (a) immune complexes, (b) hypoxia, (c)
hypercoagulability and (d) carcinomatosis
o Immune complexes: Libman-Sacks endocarditis is the prototype
o Hypoxia: studied by Nakanishi et al. in a rodent model ( Virchows Arch 1998;433:375)
o Hypercoagubility: Trousseau first noted the association between thrombosis and
malignancy
 Histological evidence of disseminated intravascular coagulopathy (DIC) has
been found in 50% patients with NBTE
o Carcinomatosis: mucin producing adenocarcinoma from the gut, lung and ovary and
acute promyelocytic leukemia are commonly associated with NBTE
Risk Factors
 Advanced stage malignancy: solid organ or hematological
 Chronic diseases: tuberculosis, uremia, AIDS
 Connective tissue disorders with hypercoaguable state: SLE patients with APLA positive
 Trauma from indwelling pulmonary catheter or central venous catheter, snake bite, late effect
of radiation therapy

Clinical features
 There are no pathognomonic signs and symptoms that allow for the confident diagnosis of
NBTE
  Patients can present with:
o Cardiac failure
 Secondary to valvular dysfunction (most commonly mitral
regurgitation), leading to dyspnea, orthopnea, paroxysmal nocturnal
dyspnea, peripheral edema, lethargy
o Cerebrovascular embolism
 Focal weakness or numbness, visual loss, dysphasia, dysarthria,
dysphagia, memory loss
o Systemic thromboembolism
 Pain, coldness and numbness of the peripheries, or acute abdominal
syndromes with pain and vomiting
o Secondary infective endocarditis
 Fever, weight loss, night sweats, lethargy, chest pain
Diagnosis
 Requires a high degree of clinical suspicion in a patient treated for infective endocarditis (IE)
and not clinically improving
 Mckay and Wahler proposed a triad for diagnosis of NBTE:
1. Presence of a disease process known to be associated with NBTE
2. Presence of heart murmur and
3. Evidence of multiple systemic emboli
 Main differential diagnosis is Infective endocarditis - distinction is important
Laboratory
 Exclude DIC: full blood count, prothrombin time, partial thromboplastin time, fibrinogen,
thrombin time, D dimers and cross linked fibrin degradation products
o These may be normal, but in the presence of risk factors, an abnormal result
should alert the physician to a diagnosis of NBTE
 Multiple blood cultures to rule out any infective cause
 Immunological assays for antiphospholipid syndrome (APS)
 Polymerase chain reaction (PCR) for rapid and reliable detection of culture negative
endocarditis by fastidious organisms
Radiology description
 Transoesophageal echo (TEE) has a higher sensitivity (90%) than transthoracic echo (TTE),
especially for vegetations of < 5 mm
 Cardiac MRI using TrueFISP gradient echo sequence allows the morphology of small heart
structures such as valves to be examined in detail ( J Comput Assist Tomogr 1996;20:613)
 Diffusion weighted MRI (DWI) can differentiate cardioembolic stroke caused by infective
endocarditis from that of NBTE due to the lack of a cellular component in NBTE emboli
Prognostic factors
 Dependent on underlying disease activity and associated renal and myocardial dysfunction
Treatment
 Treatment is difficult - correction of the underlying cause is of paramount importance
  In patients with potentially curable cancer, coagulopathy should be corrected and, if there is
no contraindication, these patients should be anticoagulated with heparin
 There are no guidelines for surgical intervention in patients with NBTE - decision is based
upon individual case
Gross description
 NBTE vegetations are typically small, friable, white or tan masses, < 1 cm in diameter, broad
based and irregular, usually along lines of valve closure on leaflets which may be normal
or previously damaged
 Vary from tiny lesions to large and exuberant masses
 Based on morphology, Allen and Sirota proposed a macroscopic classification of NBTE:
o Type 1:
 Small, < 3 mm univerrucal, firmly attached to the valve
o Type 2:
 Large, > 3mm univerrucal, adherent to the valve
o Type 3:
 Small, 1 - 3mm multiverrucal, friable
Microscopic (histologic) description
 NBTE consists of degenerating platelets interwoven with strands of fibrin and forming a
bland, featureless eosinophilic mass except for a few trapped leucocytes
 Three stages have been described in the evolution of NBTE vegetations: ( eMedicine: Libman-
Sacks Endocarditis Workup [Accessed 28 February 2018])
o Active verrucae: Consist of clumps of fibrin on and within the valvular leaflet
tissue which is focally necrotic, with plasma cells and lymphocytes
o Combined active and healed lesions: Contain vascularized, fibrous tissue
adjacent to fibrinous and necrotic areas
o Healed lesions: Consist of dense, vascularized, fibrous tissue
Differential diagnosis
 Infective endocarditis

Libman–Sacks endocarditis
Libman–Sacks endocarditis (LSE)
is a form of non-bacterial endocarditis that is seen in association with systemic lupus erythematosus
(SLE), antiphospholipid syndrome, and malignancies. It is one of the most common heart-related
manifestations of lupus (the most common being pericarditis)
Causes
LSE occurs in association with systemic lupus erythematosus, antiphospholipid syndrome,
and malignancies
In SLE, LSE has been linked to pericarditis, presence of anticardiolipin antibodies, arterial and venous
thromboses, and neuropsychiatric manifestations of SLE. LSE is associated with greater SLE duration
and severity. In some cases, LSE may be the presenting pathology in SLE, especially in the presence of
concurrent antiphospholipid syndrome.
Pathophysiology
The initial cause of LSE is poorly understood. LSE is thought to occur in the context of a hypercoagulable
state which leads to endothelial injury and subsequent deposition of thrombi and inflammatory molecules
in affected valves. The vegetations that are thus formed consist of immune complexes, platelet thrombi,
fibrin, and mononuclear cells. The vegetations may dislodge and cause embolisms.

Histopathology

LSE involves formation of cardiac lesions that may take the form of vegetations or thickening of the
valvular leaflets.
The vegetations are small and formed from strands of fibrin, neutrophils, lymphocytes, and histiocytes.
[5] Vegetations are most often small-to-moderate in size (<10mm), but may sometimes be large
(>10mm).
The mitral valve is typically affected, and the vegetations occur on the ventricular and atrial surface of the
valve.
Though the left-sided heart valves (mitral and aortic) are most commonly affected, any of the heart valves
as well as adjoining structures may become involved.
Libman–Sacks lesions rarely produce significant valve dysfunction and the lesions only rarely embolize.
 However, there is data to suggest an association between Libman–Sacks endocarditis and a higher risk
for embolic cerebrovascular disease in people with SLE.
The following signs of ventricular enlargement and cardiac failure may be noted in Libman-Sacks
endocarditis:

 Tachypnea and cyanosis.

 Pulse - Plateau pulse, low-volume pulse, pulsus alternans.
 Jugular venous distention.
 Displaced apex beat.
 Third and/or fourth heart sounds.
 Pulmonary rales.
 Congestive hepatomegaly.

Diagnosis
LSE should be considered in instances of thromboembolic event in persons with underlying pathology
that is associated with LSE. LSE is diagnosed with echocardiography. Other potential etiologies
(e.g. infective endocarditis) should be excluded through an extensive assessment (complete blood count
and metabolic panel, blood cultures). LSE can also be identified post-mortem during an autopsy.

Echocardiography
Echocardiography is considered the primary evaluation for LSE; transesophageal echocardiography
(TEE) has greater sensitivity and specificity than transthoracic echocardiography (TTE).
 In case of a negative TTE in the presence of clinical signs of LSE, TEE may be attempted to confirm the
presence of the condition
Vegetations of the cardiac valves and endocardium are characterised by irregular borders, heterogenous
echo density, and an absence of independent motion. Vegetations are usually small, but may be as large
as 10mm. The basal and middle portions of the mitral and aortic valves are most commonly involved.
Leaflet thickening or regurgitation may be present. There may be other carciac pathology related to the
underlying cause (SLE).

Differential diagnosis

Differential diagnoses include: rheumatic valvular disease, atrial myxoma, degenerative valvular disease,
infective endocarditis, vasculitis, cholesterol emboli syndrome, fibroelastoma, and Lambl's excrescences.

Management/treatment

The condition should be monitored to follow the development of the vegetations, and health personnel
should be conscious of the potential risks associated with the condition.
There is a paucity of empirical evidence on treatment options for persons with LSE, and treatment should
focus on the underlying cause. Anticoagulant treatment is recommended in cases with previous
thromboembolic event for prevention of subsequent occurrences. Surgical intervention may be indicated
in case of significant valvular dysfunction.
Prognosis
LSE is often associated with considerable morbidity and mortality.

Mitral Valve Prolapse

Mitral valve prolapse  is a common cause of a heart murmur caused by a
"leaky" heart valve. Most cases of mitral valve prolapse are not serious and
only need to be monitored.
Mitral valve prolapse is associated with many other symptoms and
conditions. But experts aren't sure that mitral valve prolapse is what causes
them.
What Is Mitral Valve Prolapse?

The mitral valve is a valve that lets blood flow from one chamber of

the heart, the left atrium, to another called the left ventricle. In mitral valve
prolapse, part of the mitral valve slips backward loosely into the chamber
called the left atrium. This happens when the main heart muscle, called the
left ventricle, squeezes during each heartbeat. Mitral valve prolapse differs
from mitral valve stenosis. In mitral valve stenosis, the mitral valve is stiff
and constricted.

In mitral valve prolapse, the valve slips backward due to the abnormal size
of or damage to the mitral valve tissues. For most people with mitral valve
prolapse, the cause is unknown.

Mitral valve prolapse can run in families. It can also be caused by

conditions in which cartilage is abnormal (connective tissue disease).
Nearly 8 million people in the U.S. have mitral valve prolapse.
Symptoms of Mitral Valve Prolapse

Most people with mitral valve prolapse have no symptoms. They also
never experience any health problems due to mitral valve prolapse.
Chest pain is the most frequent symptom in people who have symptoms
with mitral valve prolapse. The chest pain may be very bothersome and
frightening, but it does not increase the risk of heart attack, death, or other
heart problems.

Mitral valve prolapse is a common cause of mitral regurgitation. That's a

condition in which some blood flows backward through the mitral valve
with each heartbeat. Over years, moderate or severe mitral regurgitation
can cause weakness of the heart muscle, known as congestive heart failure.
Symptoms of congestive heart failure include:

 Shortness of breath with exertion

 Swelling in the legs and feet

Mitral valve prolapse has also been associated with other symptoms:

 Fluttering or rapid heartbeat called palpitations

 Shortness of breath, especially with exercise
 Dizziness
 Passing out or fainting , known as syncope
 Panic and anxiety
  Numbness or tingling in the hands and feet

When these symptoms occur together, they are sometimes called mitral
valve prolapse syndrome. However, experts don't know if mitral valve
prolapse itself causes these symptoms. Since these symptoms and mitral
valve prolapse are so common, they could often occur together by chance.
Diagnosis of Mitral Valve Prolapse

A doctor may suspect mitral valve prolapse after listening to someone's

heart with a stethoscope. The abnormal movement of the mitral valve can
make a distinct sound, called a "click." If mitral regurgitation is also
present, a doctor may hear a heart murmur caused by the backward flow of
blood.
Definite diagnosis of mitral valve prolapse requires an echocardiogram,
which is an ultrasound of the heart. A doctor can watch the abnormal valve
movement on a video of the beating heart. Mitral regurgitation, if present,
will also be seen with an echocardiogram.
Treatment of Mitral Valve Prolapse

Mitral valve prolapse causes no problems for most people, so treatment is

usually not needed.
People who develop severe mitral regurgitation due to mitral valve
prolapse often can benefit from surgery to repair or replace the leaky valve.
For people with symptoms of congestive heart failure caused by mitral
valve prolapse with mitral regurgitation, surgery is usually the best
treatment.
If no mitral regurgitation is present on echocardiogram, symptoms of
mitral valve prolapse rarely pose any risk. The best treatment for each
person may vary, but can include:

 Exercise
 Pain relievers
 Relaxation and stress reduction techniques
 Avoidance of caffeine and other stimulants
Beta-blockers, which are medications to slow the heart rate, may be
helpful in people who have episodes of palpitations with a rapid

Complications of Prosthetic Heart Valves

Severe Complications of Prosthetic Valves

Early Complications. Early complications are those occurring within four weeks of valve
replacement. The most dangerous situation in the early post-operative period is cardiac
tamponade. Patients may have bleeding or inflammation leading to a pericardial
effusion. If the effusion develops over several days or weeks, the patient may also have
hepatic congestion leading to improper metabolism of warfarin and subsequent
warfarin toxicity. Obviously, this situation is an immediate, life-threatening emergency.
The best solution is to have a cardiothoracic surgeon take the patient emergently to the
operating room. In those uncommon instances when the patient is in extremis,
intervention in the emergency department may be indicated. While emergency
physicians are most commonly trained to perform needle pericardiocentesis, patients
with recent valve replacement are likely to have blood and clots in the pericardial space
that are too large to aspirate with a needle.

If needle pericardiocentesis is unable to remove enough blood to temporarily stabilize a

patient in profound shock, the following aggressive approach may be lifesaving while
awaiting the arrival of the cardiothoracic surgeon or if one is not available. Open the
lower two centimeters of the midline incision by cutting the fascial sutures. Then, gently
insert a gloved finger through the thin layers of fascia and into the pericardium, taking
care to stay on the diaphragm along the back of the sternum. At this point, it should be
possible to remove enough fluid to relieve the tamponade. If not, it may also be
necessary to gently sweep a finger around the heart in the pericardial space to release
loculations of fluid that may be preventing the heart from filling. A Yankauer suction tip
may also be placed into the space after a plane is developed. The patient will likely need
simultaneous vasopressor support with catecholamines, aggressive volume
resuscitation, correction of acid-base derangements, and airway management. The
wound should be packed with povidone-iodine soaked gauze and an occlusive dressing
before the patient is transferred or taken to the operating room for definitive
management.

Concomitant reversal of any anticoagulation is indicated, but should not delay the
transfer of the patient to the operating room, since a pericardial window can be placed
with very little blood loss. While it is reasonable to provide these patients with
immediately available fresh frozen plasma, platelets, and packed red blood cells, the
physician should not administer vitamin K. It has no immediate effect and will make it
difficult or impossible to maintain appropriate anticoagulation in the post-operative
period.

Another early complication of prosthetic valve placement is new or recurrent atrial

fibrillation. Careful attention to anticoagulation and rate control is required, since many
patients who undergo valve replacement have limited cardiac reserves.

Another complication of prosthetic valves that may cause fever in the early post-
operative period is postpericardiotomy syndrome, a condition similar to Dressler's
syndrome. The condition is related to the activation and release of cytokines that
produces a generalized inflammatory state. It may cause low-grade fever, night sweats,
or difficulties with thermoregulation (patients rapidly get hot, then cold), flu-like
symptoms, and fluid retention. Patients are prone to atrial arrhythmias and have
elevated markers of inflammation such as C-reactive protein and erythrocyte
sedimentation rate. Because patients with this condition retain fluid and have chest
radiograph appearances similar to congestive heart failure, they often are misdiagnosed
as such. Patients with this syndrome should be treated with diuretics, nonsteroidal anti-
inflammatory drugs (NSAIDs) if they are not on warfarin, and reassurance that they will
improve. Patients should be monitored for atrial arrhythmias. While the syndrome can
have a relapsing course, it usually spontaneously resolves with a favorable
prognosis.25 In severe cases or in patients who are unable to take NSAIDs, a short
course of tapering steroids may be beneficial.

A common complaint of patients presenting to the emergency department after cardiac

surgery is chest pain. While evaluation for myocardial infarction is appropriate in those
with accompanying coronary artery disease, one should remember that cardiac
biomarkers may remain elevated for several days after major cardiac surgery. The most
common cause of chest pain is noncompliance with the analgesic prescribed.

Late Complications. While patients are at highest risk for problems during the first
month following surgery, complications may develop at any time. The most common
late problems are related to anticoagulation. Patients will either have a spontaneous or
traumatic hemorrhage, or they are not sufficiently anticoagulated and have a
thromboembolic event. While thrombus on the valve is of concern and potentially
deadly, a thromboembolic event at a distant location such as the brain, kidneys, or lower
extremities may be the first sign of an intracardiac thrombus.

Other complications of patients with prosthetic valves include late-onset atrial

fibrillation and endocardial infection. Patients with prosthetic valves, especially those in
the mitral position, are at higher risk for atrial fibrillation for the rest of their lives. Even
patients with a bioprosthetic valve may require anticoagulation if they develop atrial
fibrillation. While the highest risk for infectious endocarditis is in the early post-
operative period, there is a continual long term risk that the valve will be
hematogenously seeded.

Infectious Endocarditis

One of the deadliest complications of prosthetic valves is infectious endocarditis. In

addition to the presence of a foreign body, patients with prosthetic valves have frequent
hematogenous exposures through multiple arterial or venous puncture sites. Multiple
blood cultures should be considered during febrile illnesses prior to the administration
of antibiotics (ideally, the first and last samples should be drawn from different sites at
least one hour apart).26-28

Endocarditis in patients with prosthetic valves accounts for 15% of all endocarditis
cases and can be divided into early and late endocarditis.13 Early prosthetic valve
endocarditis occurs within six months of implantation and is most commonly caused
by Staphylococcus epidermidis, gram-negative bacteria, or fungi. Late prosthetic valve
endocarditis is any infection occurring six months or more after implantation. The
bacteria involved are the same as those seen in native valve endocarditis,
including Staphylococcus aureus, Streptococcus viridans, Enterococcus, Streptococcus
bovis, Haemophilus parainfluenza, Haemophilus aphrophilus, Actinobacillus
actinomycetemcomitans, Cardibacterium hominis, Eikenella corrodens, and Kingella
kingae (HACEK organisms).28 Even with aggressive therapy, the mortality rate of
infectious endocarditis may be as high as 80% for early endocarditis and as high as 50%
for late endocarditis.29
Patients with endocarditis most commonly present with fever and malaise. They also
may have complaints of dyspnea, chest pain, neurologic symptoms or other signs of
systemic emboli. Because patients with prosthetic valves and endocarditis are at risk
for mycotic cerebral aneurysms, brain imaging is recommended. Laboratory
abnormalities in patients with endocarditis, such as an elevated white blood cell count,
C-reactive protein, or erythrocyte sedimentation rate, are nonspecific and common to
other infectious processes. These patients often have microscopic hematuria from
emboli to the kidneys and may be mildly anemic.

The diagnosis of prosthetic valve endocarditis may be difficult. Two positive blood
cultures from different sites are definitive, but endocarditis may exist with negative
blood cultures. The presence of vegetations on the valve(s) also confirms the diagnosis,
but visualization of them may require TEE. It is rare to visualize vegetations on the disks
of prosthetic valves, but paravalvular abscesses may be identified as echo-dense or
echo-lucent areas adjacent to the valve sewing ring.

If prosthetic valve endocarditis is suspected, broad-spectrum antibiotics should be

started as quickly as possible after cultures are obtained. A cardiothoracic surgeon
should be consulted as soon as possible. Prompt surgical therapy is recommended
because delay is associated with further tissue destruction, systemic embolic events,
and hemodynamic decompensation.13

Antimicrobial Therapy for Endocarditis

The presence of a prosthetic valve creates areas of stagnant blood flow that may lead
to thrombus and/or vegetation formation. These structures sequester bacteria from the
bloodstream, so long durations of antibiotic therapy are necessary. Parenteral therapy is
preferred because sustained, high, predictable bloodstream levels of antibiotics are
required. Because of the duration of therapy, levels of vancomycin and aminoglycosides
should be monitored.14

Staphylococcus aureus is now the most common organism causing endocarditis, but
empiric therapy in the emergency department — if the diagnosis is suspected and
therapy initiated — should be broad spectrum, including coverage for gram-positive
bacteria and gram-negative bacteria. Commonly, a beta-lactam or vancomycin is used
in combination with an aminoglycoside. Theoretically, cell wall active agents such as
beta-lactams and vancomycin provide increased entry of aminoglycosides into bacterial
cells, thereby increasing their efficacy.14,15 For suspected prosthetic valve endocarditis,
an example antibiotic regimen would be vancomycin, loading dose 15 mg/kg followed
by 500 mg every six hours, plus gentamicin 1-3 mg/kg loading dose followed by 1
mg/kg every 8 hours. Alternatively ceftriaxone 1-2 g every 12 hours could be used
instead of vancomycin.27,28,30 Expert consultation regarding antibiotic selection should be
sought.

Thromboembolic Complications

Neurologic events in patients with prosthetic valves should be considered to be valve-

related until proven otherwise. Thromboembolic events are estimated to occur at a rate
of 0.6% to 2.3% per patient year.5,13 The rate of events for patients with mechanical
valves on anticoagulation therapy is similar to that of patients with bioprosthetic valves.
The rate of thromboembolic events varies as well with other risk factors such as atrial
fibrillation or left ventricular dysfunction. Systemic emboli may arise from either
obstructing or nonobstructing thrombosis, but patients with nonobstructing thrombus
more commonly present with systemic symptoms. In addition, most patients with a
thromboembolic event are found to be inadequately anticoagulated.

Treatment of ischemic strokes should begin with determination of the adequacy of

anticoagulation. If it is suboptimal, therapy should be reinstituted or adjusted to
maintain therapeutic effect. If anticoagulation has been adequate, aspirin should be
started as well as raising the target INR. Given the need to maintain anticoagulation, it is
important to monitor patients carefully for hemorrhagic transformation of an ischemic
stroke. In cases of thromboembolic stroke, thrombus may not be visualized on the valve
because of the limitations of echocardiography, small size of the thrombus, or the fact
that the thrombus is no longer there.31,32 The intestines, kidneys, and other solid organs
are other possible sites of thromboembolism.

Valve Obstruction

Prosthetic valves may become obstructed due to thrombosis, pannus formation, or a

combination of both. Valve thrombosis may be obstructive or non-obstructive.
Thrombosis may occur slowly as a chronic progressive worsening of function or may
occur more acutely. Inadequate anticoagulation is almost always associated with left-
sided heart valve thrombosis.3,6,7

Patients with obstructive valve thrombosis typically present with acute pulmonary
edema, dyspnea, cardiogenic shock, or systemic thromboembolism. New murmurs or
muffled heart sounds may be heard. A patient with a mechanical prosthetic valve and
severe acute congestive heart failure who does not have a distinct click on physical
examination should prompt the consideration of valvular obstruction. While prosthetic
valve thrombosis can be identified with transthoracic echocardiography and
fluoroscopy about 85% of the time, TEE remains the most sensitive test32 and is
essential for valves in the mitral position, yet may be difficult to obtain in urgent and
emergent fashion.

Treatment of valve thrombosis is controversial. Some surgeons recommend

thrombolytics as first-line agents.17,20-22 Success rates range from 71-88%, with rates of
significant bleeding or embolism 15-25%. Mortality rates from thrombolytic therapy are
estimated to be 3-12%, but that remains lower than the 12-46% mortality rate for valve
thrombosis surgery. Proponents of early surgical intervention argue that the 25%
chance of a cerebral vascular accident, many of which are large, hemiplegic strokes, is
much too high of a risk to warrant the use of thrombolytics in patients with left-sided
valve thrombosis. They also argue that patients who develop thrombus on a prosthetic
valve once are at a higher risk for recurrence and opt to debride the thrombosed valve or
replace it with a less thrombogenic one.18,23,24 The benefit-to-risk ratio, however, may be
more in favor of thrombolytic therapy for patients with right-sided valve thrombosis as
compared to left-sided valve thrombosis, since embolization to the lungs is less likely to
have devastating long-term consequences than embolization to the brain.

Valve obstruction due to tissue overgrowth (pannus formation) with or without

thrombus at the annulus is another cause of stenosis or regurgitation. The pannus may
block the normal opening and closing of the valve.

Prosthetic valve stenosis from pannus formation or thrombus presents with signs and
symptoms similar to native valve stenosis. Prominent symptoms may include dyspnea
and angina. Patients with prosthetic mitral valve stenosis may present with acute
pulmonary edema or, if the condition develops chronically, hemoptysis and pulmonary
hypertension. Electrocardiography may show evidence of left atrial enlargement or atrial
fibrillation.

Patients with prosthetic aortic valve stenosis may have exertional syncope. New or
worsening murmurs, reports of syncope or near syncope, and worsening dyspnea
should raise suspicion for this type of valvular stenosis. The diagnosis can be
confirmed with echocardiography examining the extent of disk motion. Patients with
acute severe aortic stenosis may require gentle fluid resuscitation and inotropic
therapy. It is important to remember that these patients should not be overloaded with
fluid and that preload reduction with agents such as nitroglycerin may lead to
cardiovascular collapse.

Structural Failure

Primary structural failure of modern prosthetic heart valves is extremely rare. Most
structural failure is related to complications that occur at the interface of the valve and
the native tissues.3,6,7 As in other complications, it may be an acute or slowly progressive
disease process. Paravalvular regurgitation may be due to dehiscence, infection, or
fibrosis and calcification of the native annulus, leading to inadequate contact between it
and the sewing ring.33

Prosthetic valve regurgitation also presents similarly to native valve regurgitation.

Regurgitation may be paravalvular or as a result of leaflet or disk deterioration.
Bioprosthetic valves located near calcified nodules resulting from endocarditis are
particularly vulnerable to regurgitation. Severity of chronic regurgitation may be
quantified by echocardiography, and patients should be monitored at least annually for
worsening.

Acute mitral valve regurgitation causes fulminant pulmonary edema and hemodynamic
collapse. Chronic mitral valve regurgitation may produce fatigue and dyspnea on
exertion, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema. Stabilization
of the patient in the acute setting focuses on treatment of the pulmonary edema with
nitrates, morphine, and diuretics. In a severely hypotensive patient, placement of an
intra-aortic balloon pump may be considered in addition to catecholamime and
ventilatory support.

Aortic valve regurgitation also may cause dyspnea, tachypnea, and chest pain. Acute
aortic regurgitation is a surgical emergency. Afterload reducers such as nitroprusside
may help stabilize the patient until surgical intervention and valve replacement are
possible.27

Rare Complications

Patient–Prosthesis Mismatch. In spite of careful evaluation and planning by a

cardiothoracic surgeon, rarely the functional area of a prosthetic valve may be too small
for the cardiac demands of a particular patient. This phenomenon is termed patient-
prosthesis mismatch. Severe aortic valve patient-prosthesis mismatch is associated
with a mortality rate of up to 10 times higher than those with an adequate functional
valve area.34-36 This difficulty can become apparent in the early and late post-operative
period principally as heart failure.

Hemolytic Anemia. While the vast majority of patients with prosthetic valves will have
some evidence of hemolysis, clinically significant anemia is rare without paraprosthetic
regurgitation. Most patients may be treated simply with iron and folate
supplementation, but severe, refractory anemia may require repeat valve surgery or
surgical repair of a paravalvular leak.
Pseudoaneurysm. Left ventricular pseudoaneurysm is a rare complication of mitral
valve replacement that occurs in up to 0.5% to 2.0% of cases.37 Unlike a true aneurysm,
these pouches contain no myocardial cells. These pseudoaneurysms are typically
associated with infection. Most frequently, the pseudoaneurysm will develop at the
posterior annular suture line and can be diagnosed with echocardiogram. Left
ventricular pseudoaneurysm requires surgical repair because it may rupture.
Additionally, a pseudoaneurysm may form in the mitral aortic intervalvular fibrosa,
creating a pouch between the posterior root of the aorta and the left ventricle. 34

Chronic Management Issues

Recommendations for Anticoagulation in Patients with Valvular Replacement. The

American College of Cardiology, American College of Chest Physicians, and American
Heart Association have created guidelines for anticoagulation of patients with
prosthetic valves.10 Patients with mechanical valves in the mitral position should be on
warfarin with a goal INR of 2.5-3.5. Patients with mechanical valves in the aortic
position should be anticoagulated to the same degree as those with mitral valves if the
valve is a caged-ball or tilting disk valve. Bileaflet valves in the aortic position require
warfarin, but with a lower goal INR of 2.0-3.0. Patients who fail anticoagulation or have
other risk factors also may be maintained on daily aspirin. Aspirin therapy is
recommended for all patients with mechanical valves by the American College of
Cardiology and American Heart Association, but the possible risk of increased bleeding
led the American College of Chest Physicians to recommend that the dual therapy be
utilized only for patients with additional risk factors or those who fail warfarin therapy
alone.10 (See Figure 7.)
Patients with bioprosthetic valves in the aortic position are recommended to have
aspirin daily for three months, and possibly be maintained on aspirin therapy for life. It is
recommended that patients with bioprosthetic valves in the mitral position, and
sometimes in the aortic position, should be anticoagulated with warfarin for three
months with a goal INR of 2.5-3.5. These patients may or may not be maintained on
lifelong aspirin therapy.10 In addition, many patients will have co-existing coronary artery
disease or atrial fibrillation and will be maintained on clopidogrel or warfarin
respectively, independent of their prosthetic valve.

Antibiotic Prophylaxis. In 2007, the American Heart Association and American College
of Cardiology issued updated guidelines regarding the use of prophylactic antibiotics for
invasive procedures in patients with prosthetic heart valves. These guidelines changed
the previous recommendations for prophylactic antibiotics for all invasive dental,
respiratory, abdominal, and genitourinary procedures. Their current recommendations
are to provide prophylaxis for patients with prosthetic heart valves undergoing: high-risk
procedures including dental procedures that involve perforation of the oral mucosa or
manipulation of the gingival tissue or periapical region of teeth; and invasive procedures
of the respiratory tract that involve biopsy or incision. These changes in the guidelines
were prompted by a lack of evidence demonstrating the effectiveness of more liberal
prophylaxis. In addition, there were concerns about adverse reactions related to
antibiotic usage such as allergic reactions, development of antibiotic resistance, and
severe side effects. It is noteworthy that these same guidelines also significantly reduce
the number of cardiac conditions for which antibiotic prophylaxis is recommended.

The AHA/ ACC guidelines, however, remain controversial. The Australian guidelines for
the prevention of endocarditis, the British Society of Antimicrobial Therapy, and the
European Society for Cardiology all continue to recommend antibiotic prophylaxis for
most or all invasive dental, gastrointestinal, respiratory, and genitourinary procedures
that involve trauma to mucosal surfaces.15,38,39 The National Institute for Health and
Clinical Excellence recommends prophylaxis for invasive genitourinary or
gastrointestinal procedures at the site of known infection.40 Proponents of more liberal
use of prophylactic antibiotics suggest that the lack of randomized controlled trials to
support the practice does not necessarily invalidate the benefit of antibiotics, and they
suggest that the risk of antibiotic usage was considered in prior risk-benefit analyses
leading to previous guidelines. In addition, they believe that infectious endocarditis has
such a high morbidity and mortality rate that even a small reduction in the likelihood of
developing the disease warrants the utilization of antibiotics.

From the standpoint of an emergency physician, it is important to understand the

controversy in order to educate patients, and to understand that patients with prosthetic
valves are considered at high risk for the development of infectious endocarditis by all
of the aforementioned expert panels. Therefore, all patients with prosthetic valves
undergoing a procedure manipulating the gingival tissue (such as a mandibular nerve
block or drainage of an oral abscess) in the emergency department should be provided
antibiotic prophylaxis. In addition, the emergency department physician should consider
prophylaxis in any patient with a prosthetic valve undergoing procedures violating the
mucosal barrier in the respiratory, gastrointestinal, or genitourinary tracts (such as
those undergoing endoscopy where biopsies will be taken) or trauma with significant
skin contamination. Prophylaxis is not needed for endotracheal intubation, insertion of
urinary catheters, vaginal delivery, endoscopy without biopsy, uterine dilation and
curettage, or insertion/removal of an intrauterine device.

Typically, antibiotic prophylaxis for dental procedures consists of 2 g of amoxicillin

given by mouth one hour prior to the procedure, or 600 mg clindamycin given orally or
intravenously one hour prior to the procedure for patients who are penicillin-allergic.
Patients who are unable to take oral medications may be administered 2 g of ampicillin
intravenously, also administered one hour prior to the procedure.41

Summary