1

Case Report
Post Op Pericardial Effusion ec RHD
Presenter

: Ramos
Dina Utami

Supervisor

(100100125)
(100100160)

: dr. Muhammad Ali, Sp.A (K)

INTRODUCTION
Acute rheumatic fever (ARF) is an auto-immune consequence of infection with the
bacterium group A streptococcus (GAS). It causes an acute generalised inammatory
response and an illness that aects only certain parts of the body mainly the heart,
joints, brain and skin. Individuals with ARF are often severely unwell, in great pain,
and require hospitalisation. Despite the dramatic nature of the acute episode, ARF
leaves no lasting damage to the brain, joints or skin. Acute rheumatic fever (ARF) is an
illness caused by a reaction to a bacterial infection, which often results in lasting
damage to heart valves. This is known as rheumatic heart disease (RHD) and it is an
important cause of premature mortality. Almost all cases of RHD and associated deaths
are preventable. However, ARF and RHD remain common in many developing
countries. RHD is the most frequent form of heart disease in children worldwide.1
Acute rheumatic fever is a non-suppurative complication of group A beta hemolytic
streptococcal (GABHS) sore throat. It affects joints, skin, subcutaneous tissue, brain
and heart. Except heart, all other effects are reversible, needing only symptomatic relief
during the episodes. Cardiac complications are significant in absence of secondary
prophylaxis and culminate into chronic and life threatening valvular heart disease. 2
The only cost-effective approach to controlling RHD is secondary prophylaxis in the
form of penicillin injections every 34 weeks to prevent recurrent attacks of group A
streptococcal infection that cause ARF and, thus, the worsening of RHD. However, the
majority of patients who enroll into register-based programs are symptomatic with
advanced disease, indicating that they have had a number of silent or undetected attacks
of ARF. Patients with mild, asymptomatic RHD have the most to gain from second- ary
prophylaxis because, in the absence of ARF recurrence, the majority will have no

detectable disease within 510 years. Screening to detect asymptomatic cases is,
therefore, an attractive strategy. 3
Traditionally, RHD was diagnosed by auscultating for a heart murmur in those with a
history of ARF. Until the past decade, the stethoscope was the only noninvasive
diagnostic tool available to physicians in low-income countries and in remote settings
where ARF and RHD are most prevalent. However, detection rates were usually low.
Echocardiography has proven to be more sensitive and specific than auscultation. RHD
detected on echocardiography without an associated clinically pathological cardiac
murmur is referred to as subclinical RHD.With the advent of portable technology,
echocardiography can now be performed at a relatively low cost, eve n in remote
settings. This development raises the possibility that people with previously
undiagnosed RHD, including those without a known history of ARF, can be diagnosed
and secondary prophylaxis started at an earlier stage of the illness than previously
possible, thus potentially reducing morbidity and mortality.3
ETIOLOGY
Rheumatic fever results from an inflammatory reaction to certain group A streptococcus
bacteria. The body produces antibodies to fight the bacteria, but instead the antibodies
attack a different target: the body's own tissues. The antibodies begin with the joints and
often move on to the heart and surrounding tissues. Because only a small fraction (fewer
than 0.3%) of people with strep throat ever contract rheumatic fever, medical experts
say that other factors, such as a weakened immune system, must also be involved in the
development of the disease.4
PATHOGENESIS
Interactions involving streptococci and the host play an essential pathogenetic role for
RF occurrence. Of the -hemolytic streptococci that can produce infection in humans,
only those belonging to group A can lead to RF, almost exclusively after tonsillitis or
pharingitis. One of the first mechanism proposed to explain injury in RF was a direct invasion of the affected tissue by the Streptococcus. Evidence of a latency period of about
3 weeks between the acute streptococcal in- fection and the clinical appearance of tissue
injury suggests that tissue damage is mediated by an immunological reaction with an

autoimmune component. Kaplan and his coworkers have proposed the concept of
antigenic mimicry: antibodies produced by the streptococcal infection against the
bacterial antigens cross-react with the host tissues leading to tissue injury. The
description of the immunologic cross-reactivity between the M protein and myocardial
sarcolemma lends support to this concept. After the immune reaction there is a
subsequent inflammatory process involving myocardium and valvular endocardium.
With progression and persis- tence of inflammation valve fibrosis and cal- cification
might occur. It is extimated that only 0.3% of individuals with an untreated
streptococcal pharyngitis will present an episode of RF. Moreover RF incidence following pharyngitis in patients who have had a previous episode of RF is approximately
50%. This observation, together with clinical studies indicating a familiar clustering of
the disease, suggests that genetic factors might play a role in the susceptibility to RF. It
has been reported the presence of specific B-cell alloantigen in the 99% of patients with
RF and in only 14% of controls. Genetic susceptibility to RF is also supported by the
associa- tion with HLA-DR2 and DR4 antigens. 5
The pathogenesis of rheumatic heart disease results from an immune response
consisting of humoral and cellular components after exposure to Streptococcus
pyogenes (classified as a group A streptococcus by the Lancefield system), usually after
a throat infection. The precise pathophysiology is obscure but several advances have
now been reviewed. Antigenic mimicry in association with an abnormal host immune
response is the cornerstone of pathophysiology, based on the triad of rheumatogenic
group A streptococcal strain, genetically susceptible host, and aberrant host immune
response.5
Some strains are more likely to cause acute rheumatic fever than are others. S pyogenes
contains M, T, and R surface proteins, which are all associated with bacterial adherence
to throat epithelial cells. The rheumatogenicity of some streptococcus families has
traditionally been considered a feature of strains belonging to specific. M serotypes.
However, data show that rheumatogenic M serotypes were infrequently identifi ed in
communities with high burdens of acute rheumatic fever and rheumatic heart disease.
These results question the poten tial importance of other disease causing serotypes,
especially those that cause streptococcal skin infections, which might be implicated in
cases of acute rheumatic fever. In 1889, Cheadle noted that the chance of an individual

with a family history of acute rheumatic fever acquiring the disease is nearly five times
as great as that of an individual who has no such hereditary taint.Generally, HLA class
II molecules (which participate in antigen presentation to T-cell receptors) seem to be
more closely associated with an increased risk of acute rheumatic fever or rheumatic
heart disease than are class I molecules, although no single HLA haplotype or
combination has been consistently associated with disease susceptibility. The exact
molecular mechanism by which HLA class II molecules confer susceptibility to
autoimmune diseases is unknown. The role of autoimmune reactions in the pathogenesis
of acute rheumatic fever was substantiated when antibodies against group A
streptococcus reacted with human heart preparations.
After binding to the antigenic peptide, the particular HLA complexes can initiate
inappropriate T-cell activation. Molecular mimicry takes place between streptococcal M
protein and several cardiac proteins (cardiac myosin, tropomyosin, keratin, laminin, and
vimentin), and different patterns of T-cell antigen cross-recognition have been
identified. 6
CLINICAL FEATURES
Arthritis
Arthritis is the most common presenting symptom of ARF, yet diagnostically it can be
the most dicult. It is usually asymmetrical and migratory (one joint becoming
inamed as another subsides), but may be additive (multiple joints progressively
becoming inamed without waning). Large joints are usually aected, especially the
knees and ankles. Arthritis of the hip is often dicult to diagnose because objective
signs may be limited to a decreased range of movement. The arthritis is extremely
painful, often out of proportion to the clinical signs. It is exquisitely responsive to
treatment with non-steroidal anti-inammatory drugs (NSAIDs). Indeed, this can be a
useful diagnostic feature, as arthritis continuing unabated more than 3 days after starting
NSAID therapy is unlikely to be due to ARF. Equally, withholding NSAIDs in patients
with mono-arthralgia or mono-arthritis to observe the development of polyarthritis can
also help in conrming the diagnosis of ARF. In these patients, paracetamol or codeine
may be used for pain relief. Because of the migratory and evanescent nature of the
arthritis, a denite history of arthritis, rather than documentation by the clinician, is

sucient to satisfy this criterion. ARF should always be considered in the dierential
diagnosis of patients presenting with arthritis in high-risk populations. In the hospital
setting, physicians and surgeons should collaborate when the diagnosis of arthritis is
unclear. Patients with sterile joint aspirates should never be treated speculatively for
septic arthritis without further investigation, particularly in areas with high ARF/RHD
prevalence. Mono-arthritis or polyarthralgia is a common manifestation of ARF, and is
often associated with overt or subclinical carditis. In these populations, aseptic monoarthritis or polyarthralgia may be considered as a major manifestation, in place of
polyarthritis. However, alternative diagnoses should be carefully excluded. Monoarthritis may also be the presenting feature if anti-inammatory medication is
commenced early in the illness prior to other joints becoming inamed. 1
Sydenhams chorea
This manifestation aects females predominantly, particularly in adolescence. Chorea
consists of jerky, uncoordinated movements, especially aecting the hands, feet, tongue
and face. The movements disappear during sleep. They may aect one side only
(hemichorea). Useful signs include:
The milkmaids grip (rhythmic squeezing when the patient grasps the examiners
ngers)
Spooning (exion of the wrists and extension of the ngers when the hands are
extended)
The pronator sign (turning outwards of the arms and palms when held above the
head) and
Inability to maintain protrusion of the tongue.
Because chorea may occur after a prolonged latent period following group A
streptococcus (GAS) infection, the diagnosis of ARF under these conditions does not
require the presence of other manifestations or elevated plasma streptococcal antibody
titres. Patients with pure chorea may have mildly elevated erythrocyte sedimentation
rate (ESR, approx 40mm/hr), but have a normal serum C-reactive protein (CRP) level
and white cell count. Chorea is the ARF manifestation most likely to recur, and is often

associated with pregnancy or oral contraceptive use. The vast majority of cases resolve
within 6 months (usually within 6 weeks), although rare cases lasting as long as 3 years
have been documented. 1
Carditis
Although pericarditis and myocarditis may occur, cardiac inammation in ARF almost
always aects the valves, especially the mitral and aortic valves. Early disease usually
leads to valvular regurgitation. With prolonged or recurrent disease, scarring may lead
to stenotic lesions. Acute carditis usually presents clinically as an apical holosystolic
murmur with or without a mid-diastolic ow murmur (Carey Coombs murmur), or an
early diastolic murmur at the base of the heart (aortic regurgitation). The rheumatic
aetiology can usually be conrmed by a typical appearance on echocardiography.
Congestive heart failure in ARF results from valvular dysfunction secondary to
valvulitis, and is not due to primary myocarditis. If pericarditis is present, the friction
rub may obscure valvular murmurs.1
Subcutaneous nodules
These are very rare (less than 2% of cases). They are 0.52.0cm in diameter, round,
rm, freely mobile and painless nodules that occur in crops of up to 12 over the elbows,
wrists, knees, ankles, Achilles tendon, occiput and posterior spinal processes of the
vertebrae. They tend to appear 12 weeks after the onset of other symptoms, last only
12 weeks (rarely more than 1 month) and are strongly associated with carditis.1
Erythema marginatum
Erythema marginatum is also rare. As with subcutaneous nodules, erythema marginatum
is highly specic for ARF. It occurs as bright pink macules or papules that blanch under
pressure and spread outwards in a circular or serpiginous pattern. The rash can be
dicult to detect in dark-skinned people, so close inspection is required. The lesions
are not itchy or painful, and occur on the trunk and proximal extremities but almost
never on the face. The rash is not aected by anti- inammatory medication, and may
recur for weeks or months, despite resolution of the other features of ARF. The rash may
be more apparent after showering.1

Arthralgia
Arthralgia is a non-specic symptom, and usually occurs in the same pattern as
rheumatic polyarthritis (migratory, asymmetrical, aecting large joints). Alternative
diagnoses should be considered in a patient with arthralgia that is not typical of ARF.1
Fever
With the exception of chorea, most manifesta- tions of ARF are accompanied by fever.
Earlier reports of fever described peak temperatures commonly greater than 39C, but
lower grade temperatures have been described more recently. As there are no recent
data relating to fever in low-risk populations, it is recommended that an oral, tympanic
or rectal temperature greater than 38C on admission, or documented during the current
illness, should be considered as fever (Level IV, Grade C). Fever, like arthritis and
arthralgia, is usually quickly responsive to salicylate therapy.1
Elevated acute-phase reactants
Typically, ARF patients have a raised serum CRP level and ESR. The peripheral white
blood cell count is <15109/L in 75% of patients, so an elevated white cell count is an
insensitive marker of inammation in ARF. Further analysis of these data demonstrated
that less than 4% of patients with conrmed ARF, excluding chorea, had both a serum
CRP level of <30mg/L and an ESR of <30mm/hr. Therefore, it is recommended that a
serum CRP level of 30mg/L or ESR of 30mm/hr is needed to satisfy the minor
criterion of elevated acute-phase reactants. The serum CRP concentration rises more
rapidly than the ESR, and also falls more rapidly with resolution of the attack. The ESR
may remain elevated for 36 months, despite a much shorter duration of symptoms.1
Prolonged P-R interval and other rhythm abnormalities
Some healthy people show this phenomenon, but a prolonged P-R interval that resolves
over the ensuing days to weeks may be a useful diagnostic feature in cases where the
clinical features are not denitive. Extreme rst-degree block sometimes leads to a
junctional rhythm, usually with a heart rate similar to the sinus rate. Second-degree, and
even complete heart block, can occur and, if associated with a slow ventricular rate,
may give the false impression that carditis is not signicant. A small proportion had

more severe conduction abnormalities, which were sometimes found by auscultation or

echocardiography in the absence of evidence of valvulitis.1 Therefore, an
electrocardiogram (ECG) should be performed in all cases of suspected ARF If a
prolonged P-R interval is detected, the ECG should be repeated after 12 months to
document a return to normal. If it has returned to normal, ARF becomes a more likely
diagnosis. The P-R interval increases normally with age.1
DIAGNOSIS
Accurate diagnosis of ARF is important. Over diagnosis results in unnecessary
treatment over a long time, while under-diagnosis leads to further attacks of ARF,
cardiac damage and premature death. Diagnosis remains a clinical decision, as there is
no specic laboratory test. The diagnosis of ARF is usually guided by the Jones criteria
and the more recent World Health Organization (WHO) criteria.1
The Jones criteria for the diagnosis of ARF were introduced in 1944. The criteria divide
the clinical features of ARF into major and minor manifestations, based on their
prevalence and specicity. Major manifestations are those that make the diagnosis more
likely, whereas minor manifestations are considered to be suggestive, but insucient on
their own, for a diagnosis of ARF. The exception to this is in the diagnosis of recurrent
ARF.1

10

WORK UP
Throat culture
Throat culture findings for group A beta hemolytic Streptococcus are usually negative
by the time symptoms of rheumatic fever or rheumatic heart disease appear. Attempts
should be made to isolate the organism before the initiation of antibiotic therapy to help
confirm a diagnosis of streptococcal pharyngitis and to allow typing of the organism if it
is isolated successfully. 7
Rapid antigen detection test
This test allows rapid detection of group A streptococcal antigen and allows the
diagnosis of streptococcal pharyngitis and the initiation of antibiotic therapy while the
patient is still in the physician's office. Because the rapid antigen detection test has a
specificity of greater than 95% but a sensitivity of only 60-90%, a throat culture should
be obtained in conjunction with this test. 7
Antistreptococcal antibodies
The clinical features of rheumatic fever begin at the time antistreptococcal antibody
levels are at their peak. Thus, antistreptococcal antibody testing is useful for confirming
previous group A streptococcal infection. The elevated level of antistreptococcal
antibodies is useful, particularly in patients that present with chorea as the only
diagnostic criterion. Sensitivity for recent infections can be improved by testing for
several antibodies. Antibody titers should be checked at 2-week intervals in order to
detect a rising titer.7
The

most

common

extracellular

antistreptococcal

antibodies

tested

include

antistreptolysin O (ASO), antideoxyribonuclease (DNAse) B, antihyaluronidase,

antistreptokinase, antistreptococcal esterase, and anti-DNA. Antibody tests for cellular
components of group A streptococcal antigens include antistreptococcal polysaccharide,
antiteichoic acid antibody, and antiM protein antibody. 7
In general, the ratio of antibodies to extracellular streptococcal antigens rises during the
first month after infection and then plateaus for 3-6 months before returning to normal

11

levels after 6-12 months. When the ASO titer peaks (2-3 wk after the onset of rheumatic
fever), the sensitivity of this test is 80-85%. The anti-DNAse B has a slightly higher
sensitivity (90%) for detecting rheumatic fever or acute glomerulonephritis.
Antihyaluronidase results are frequently abnormal in rheumatic fever patients with a
normal level of ASO titer and may rise earlier and persist longer than elevated ASO
titers during rheumatic fever.7
Acute phase reactants
The C-reactive protein and erythrocyte sedimentation rate are elevated in rheumatic
fever due to the inflammatory nature of the disease. Both tests have a high sensitivity
but low specificity for rheumatic fever. They may be used to monitor the resolution of
inflammation, detect relapse when weaning aspirin, or identify the recurrence of
disease. 7
Heart reactive antibodies
Tropomyosin is elevated in acute rheumatic fever.

TREATMENT
Intramuscular Benzathine penicillin G and oral Penicillin V are the recommended
antimicrobial drugs for the treatment of GAS. Except in individual with histories of
penicillin allergy. 8
The oral antibiorics of choice are penicillin V and amoxicillin. Generally, 250 mg 2
times daily is recommended for most children. A dose of 500 mg 2 to 3 imes daily is
recommended for adolescents and adults. All patient should continue to take penicillin
regulary for an entire 10 day period even though they likely will be asymptomatic after
the first few days. Penicillin V is preferred to penicillin G because it is more resistant to
gastric acid. 8
Benzathine penicillin G should be considered particularly for patients who are unlikely
to complete a 10 day course of oral therapy and for patients with personal of family
histories of rheumatic fever or rheumatic heart disease or environmental factors (such as
crowded living condition or low socioeconomic status) that place them at enhanced risk
for rheumatic fever. Benzathine penicillin G should be given as a single injection in a

12

large muscle mass. This formulation is painful, injection that contain procaine penicillin
In addition to benzathine penicillin G are less painful. The recommended dosage of
benzathine penicillin G is 600.000 U IM for patient who weight 27 kg or less and
1.200.000 U for patient who weight more than 27 kg. the combination of 900.000 U of
benzathine penicillin G and 300.000 U of procaine penicillin G is satisfactory therapy
for most smaller children. The efficacy of this combination for heavier patient such as
large teenagers or adult requires further study. Allergic reactions to penicillin are more
common in adults than in children. 8
There has been no significant change in the management of acute RF in the last 50
years. Patients need penicillin to eradicate GAS present in throat. Anti inflammatory
agents - aspirin or steroids - are used to control rheumatic activity. Aspirin or steroids do
not cure RF. These suppress the inflammatory response which lasts for about 12 wk in
more than 80 per cent patients. Hence, the standard dose of aspirin (90-120 mg/kg/day)
is given for ten weeks and tapered in the next two weeks. The dose of prednisone 60
mg/day above 20 kg and 40 mg /day below 20 kg in weight is given for three weeks and
tapered in the next nine weeks. The standard 12 week course can be reduced to four to
eight weeks depending on the patients response. 6
Patients without carditis can have weekly follow up of ESR and CRP. If they normalize,
the course can be reduced to a shorter period. Aspirin is preferred over steroids as long
as the carditis is mild and the patient is not in congestive failure. However, with severe
carditis and congestive failure steroid is the drug of choice because of the more potent
suppressive effect. 6
Non-steroidal anti-inflammatory drugs (NSAIDs) have not been systematically utilized
to establish their usefulness. Immunosuppressive agents like azathioprine and
cyclosporine A have also been considered for acute rheumatic fever. Despite of the
concerns of side effects, toxicity and late onset of lymphomas with the use of these
immunosuppressive it is possible to argue that a short course of 6 to 8 wk may result in
a greater benefit than harm. However, most ethics committees will hesitate to permit
systematic testing of these agents.6
It is now well accepted that rheumatic endocarditis involving heart valves is the main
cause of morbidity and mortality in RF. Surgical management consisting of mitral
and /or aortic valve replacement in patients whose congestive failure cannot be

13

controlled by aggressive medical treatment during acute RF, is life saving. It the
congestive failure cannot be controlled with maximal medical therapy and the patient is
deteriorating due to mitral regurgitation, mitral valve replacement during active RF is
indicated. In spite of clinical evidence for active RF, the heart size returns to normal and
congestive failure disappears, confirming that rheumatic myocarditis plays little or no
role in the mortality of RF. 6
Management of chorea: It has a self limiting course, hence parents need reassurance.
The children could be reated with sedatives like phenobarbitone 30 mg thrice daily.
chlorpromazine, valium, diphendydramine or promethazine can be used as sedatives.
Haloperidol 5 to 10 mg twice daily has been used effectively. Although aspirin and
steroids are not supposed to have a place in the treatment of chorea, some patients have
shown dramatic response to steroids, if they do not show adequate response to
sedatives. 6
Since, long term follow up of chorea patients have identified subclinical carditis in 20 to
30 per cent patients, penicillin prophylaxis is essential and should be continued on a
long term basis. Rheumatic heart disease: Surgical management of valve disease was
the standard approach till balloon mitral valvotomy was introduced in 1985. Mitral
stenosis

could

be

corrected

surgically

either

by

closed

valvotomy, open

commissurotomy or by valve replacement if the valve was calcified. Balloon valvotomy

provides results as good as surgical valvotomy and has become the treatment of choice
in spite of being more expensive. For mitral regurgitation the choice of treatment would
be valve repair especially in younger patients to avoid long-term anti-coagulant therapy.
Most patients with mitral or aortic valve regurgitation end up with valve replacement.
Hence, although surgical help is very useful it is expensive and requires prolonged care
with anticoagulant therapy with the associated complications of valve thrombosis and
systemic embolic disasters especially in the low-income population of the country. Over
a long follow up period relatively few patients remain free of event. Balloon mitral
valvotomy has been utilized in the paediatric patients below 1-2 yr in age with
acceptable results. It has been extended to patients of mitral stenosis.6
PERICARDIAL EFFUSION
INTRODUCTION

14

Pericardial effusion is the presence of an abnormal amount of and or an abnormal

character to fluid in the pericardial space. It can be caused by a variety of local and
systemic disorders, or it may be idiopathic.9
Pericardial effusions can be acute or chronic, and the time course of development has a
great impact on the patient's symptoms. Treatment varies, and is directed at removal of
the pericardial fluid and alleviation of the underlying cause, which usually is determined
by a combination of fluid analysis and correlation with comorbid illnesses.9
Pericardial effusion is a common finding in clinical practice either as incidental finding
or manifestation of a systemic or cardiac disease. The spectrum of pericardial effusions
ranges from mild asymptomatic effusions to cardiac tamponade. Moreover, pericardial
effusion may accumulate slowly or suddenly.9
Unfortunately, there are few epidemiological data on the incidence and prevalence of
such effusions in the clinical setting. In Maria Vittoria hospital, an urban general ospital
in Torino and an Italian referral centre for pericardial diseases, the mean annual
incidence and prevalence of pericardial effusion have been, respectively, 3 and 9% in a
Years experience of the echo laboratory.10
Such data mainly depend on the epidemiological background (especially developed vs.
developing country, where tuberculosis is a leading cause of pericardial disease and
concurrent HIV infection may have an important promoting role), the institutional
setting (tertiary referral centre vs. secondary and general hospitals), and the availability
of specific subspecialties (especially nephrology, rheumatology, and oncology). 10
ETIOLOGY
A wide variety of aetiologic agents may be responsible of pericardial effusions, since all
known causes of pericardial disease may be causative agents. The more common causes
of pericardial effusions include infections (viral, bacterial, especially tuberculosis),
Cancer, connective tissue diseases, pericardial injury syndromes (post-myocardial
infarction effusions, post-pericardiotomy syndromes, post-traumatic Pericarditis either
iatrogenic or not), metabolic causes (especially hypothyroidism, renal failure),
myopericardial diseases (especially pericarditis, but also myocarditis, heart failure),

15

aortic diseases, especially aortic dissection extending into the pericardium, and selected
drugs (i.e. minoxidil). Hydropericardium, a non-inflammatory transudative pericardial
effusion, may occur not only in heart failure, but also syndrome, when Starling forces
promote the accumulation of a plasma ultrafiltrate across the pericardium as well as
other membranes (e.g. pleura and peritoneum). 10
In the last 20 years, five major surveys have been published on the characteristics of
moderate to large pericardial effusions. Obviously, the relative frequency of different
causes depends on the local epidemiology (especially the prevalence of tuberculosis),
the hospital setting, and the diagnostic protocol that has been adopted. Many cases still
remain idiopathic in developed countries (up to 50%), while other common causes
include especially cancer (1025%), pericarditis and infectious causes (1530%),
iatrogenic causes (1520%), and connective tissue disease (515%), whereas
tuberculosis is the dominant cause in developing countries (60%), where tuberculosis is
endemic.In the setting of pericarditis with pericardial effusion, the prevalence of
malignant or infectious aetiologies ranges from 15 to 50% depending on published
series advanced hypoalbuminaemia, such as in cirrhosis and nephritic.10

16

Table. Etiology Pericard Effusion

17

PATHOGENESIS
The normal pericardial sac contains 1050 mL of pericardial uid acting as a
lubricant between the pericardial layers. Surprisingly, little is known about the
formation and removal of pericardial uid, because of the paucity of comprehensive
studies, especially in human subjects, and methodological difculties to distinguish
between the dynamics of normal pericardial uid and those of a pathological effusion.
Nevertheless, normal pericardial uid is generally considered an ultraltrate of plasma.
The arrangement of lymphatic vessels is complex and has been described in human
cadavers. The lymphatic vessels include different pathways according to ventral, lateral,
and posterior surfaces, but, in any case, terminate to mediastinal, tracheobronchial, or
iux- taesophageal lymph nodes. On the ventral surface, the lymphatics of the parietal
pericardium connect to lymphatics in the pericardial fat and areolar tissue. On the lateral
and posterior surfaces, the lymphatics of the parietal pericardium anastomose with
lymphatics of the reected mediastinal pleura. Lymphatic drainage of the pericardium to
the mediastinal and tracheobronchial lymph nodes and interactions with pleural provide
the anatomical basis for pathological involvement of the pericardium in specic
diseases (i.e. pleuro-pulmonary diseases such as pulmonary tuberculosis and lung
cancer). 11
Any pathological process usually causes an inammatory process with the possible
increased production of pericardial uid (exudate). An alternative mechanism of the
formation of peri- cardial uid may be the decreased reabsorption due to increased
systemic venous pressure generally as a result of congestive heart failure or pulmonary
hypertension (transudate). If pericardial uid is free to move within the pericardial sac
following the gravity forces, it usually starts accumulating posteriorly to the left
ventricle when the patient is laying on his/her left side for echocardiographic evaluation
(mild effusion detected initially as posterior), then circumferentially in the case of
moderate to large pericardial effusions. A mild pericardial effusion may also be detected
close to the right atrium because this is the cardiac chamber with the lowest pressures
within the cardiac cycle and thus pericardial uid accumulation is easier in this position.
An isolated mild anterior pericardial uid is unusual on echocardiography without
previous pericardial scarring as following surgery or chronic pericarditis, and should be
regarded as fat rather than pericardial uid. 11

18

Computed tomography (CT) or cardiac magnetic resonance (CMR) may conrm the
nding in specic cases. On the contrary after pericardial scarring (i.e. after cardiac
surgery or chronic pericarditis, or bacterial infections), pericardial uid may not have a
uniform distribution within the pericardial space and may give rise to loculated
effusions that should be evaluated with multiple cardiac views. The pressure volume
curve of the normal pericardium is a J-shaped curve: after an initial short shallow
portion that allows the pericardium to stretch slightly in response to physiological
events, such as changes in posture or volume status, with minimal pressure increase,
then the pericardium does not allow further sudden increases of the volume without a
marked increase in the intrapericardial pressure. Thus a sudden increase of pericardial
volume of 100200 mL, as in haemopericardium, may elevate pericardial pressure till
2030 mmHg with acute cardiac tamponade (acute or surgical cardiac tamponade). On
the contrary a slowly accumulating pericardial uid may allow pericardial distention till
the accumulation of 12 L of pericardial uid without the development of cardiac
tamponade till advanced stages often because of intercurrent events (chronic cardiac
tamponade or medical cardiac tamponade).11
CLINICAL MANIFESTATION
The clinical presentation of pericardial effusion is varied according to the speed of
pericardial uid accumulation as mentioned in the introduction, and the aetiology of the
effusion with possible symptoms that may be related to the causative disease. The rate
of pericardial uid accumulation is critical for the clinical presentation. If pericardial
uid is quickly accumulating such as for wounds or iatrogenic perforations, the
evolution is dramatic and only small amounts of blood are responsible of a quick rise of
intrapericardial pressure and overt cardiac tamponade in minutes. On the contrary a
slowly accumulating pericardial uid allows the collection of a large effusion in days to
weeks before a signicant increase in pericardial pressure becomes responsible of
symptoms and signs. 3 Classical symptoms include dyspnoea on exertion progressing to
orthopnoea, chest pain, and/or fullness. Additional occasional symptoms due to local
compression may include nausea (diaphragm), dysphagia (oesophagus), hoarseness
(recurrent laryngeal nerve), and hiccups (phrenic nerve). Nonspecic symptoms include
also cough, weakness, fatigue, anorexia and palpitations and reect the compressive

19

effect of the pericardial uid on contiguous anatomic structures or reduced blood

pressure and secondary sinus tachycardia.10
The classical ndings of cardiac tamponade have been described by the thoracic
surgeon Beck in 1935. Beck identied a triad including hypotension, increased jugular
venous pressure, and a small and quiet heart. This triad was classically identied in
surgical tamponade with acute cardiac tamponade due to intrapericardial haemorrhage
because of trauma, myocardial or aortic rupture. The Beck triad may be lacking in
patients with medical tamponade with slowly accumulating pericardial uid.
Hypotension is absolute or relative. Acute cardiac tamponade is usually associated with
low blood pressure (90 mmHg) but may be only slightly reduced in subacute, chronic
tamponade. Hypertensive patients may have normal to mildly elevated blood pressure
concomitant to cardiac tamponade. Fever is a nonspecic sign that may be associated
with pericarditis either infectious or immunomediated (i.e. systemic inammatory
diseases).10
DIAGNOSIS
On physical examination classical signs include neck vein distention with elevated
jugular venous pressure at bedside examination, pulsus paradoxus, and diminished heart
sounds on cardiac auscultation. Pericardial friction rubs are rarely reported, they can be
usually detected in patients with concomitant pericarditis. Rubs which occur during the
maximal movement of the heart within its pericardial sac, are said to be generated by
friction between the two inamed layers of the pericardium. However, this commonly
offered explanation for its mechanism may be an oversimpli- cation as patients with a
pericardial effusion may also have an audible friction rub, and there is no precise
correlation between pericardial rubs and size of the effusion, although pericardial rubs
may be easier to hear in patients without a pericardial effusion, but this nding is not
universal and is not well documented.10
The diagnosis of pericardial effusion is generally performed by echocardiography, that
also allows the semiquantitative assessment of the pericardial effusion size and its
haemodynamic effects as outlined in the paragraph on the initial approach to pericardial
effusion.10

20

The diagnosis of cardiac tamponade is essentially a clinical diagnosis requiring

echocardiographic conrmation of the initial diagnostic suspicion. In most patients,
cardiac tamponade should be diagnosed by a clinical examination that shows elevated
systemic venous pressure, tachycardia, dyspnoea, and paradoxical arterial pulse.
Systemic blood pressure may be normal, decreased, or even elevated. The diagnosis is
conrmed by an echocardiographic demonstration of moderately large or large
circumferential pericardial effusion and in most instances, of right atrial compression,
abnormal respiratory variation in right and left ventricular dimensions, and in tricuspid
and mitral valve ow velocities usually associated with inferior vena cava.10
Nevertheless, the diagnostic work up should be guided by the epidemiology and the
clinical presentation to avoid performing an extensive and blinded testing. As already
remarked, developing countries have a high rate of pericardial effusions correlated to
tuberculosis (60 and 80% with HIV infection) 28,29 that should be ruled out in such
context, as well as in immigrants and HIV infected patients. Non idiopathic and non
viral aetiologies (especially bacterial and neoplastic) are associated with an increased
risk of cardiac tamponade and large effusion, and pericardiocentesis is mandatory when
cardiac tamponade or such aetiologies are suspected.10
Analyses of pericardial effusion can establish the diagnosis of in- fectious and
neoplastic pericardial effusions. Cytology and tumour markers [carcinoembryonic
antigen (CEA), alfafeto protein, carbohydrate antigens CA 125, CA 72-4, CA 15-3, CA
19-9, etc.) should be performed in suspected malignant disease. In suspected
tuberculosis acid fast bacilli staining, mycobacterium culture or radiometric growth
detection (e.g. BACTEC-460), adenosine deaminase (ADA), interferon (IFN) gamma,
pericardial lysozyme, and as well as PCR analyses for tuberculosis should be performed
(indication class I, level of evidence B). Differentiation of tuberculous and neoplastic
effusion is virtually absolute with low levels of ADA and high levels of CEA. In
addition, high ADA levels may predict the evolution towards pericardial constriction. In
suspected bacterial infections, at least three cultures of pericardial uid for aerobes and
anaerobes as well as the blood cultures are manda- tory (indication class I, level of
evidence B). PCR analyses for car- diotropic viruses have been suggested (indication
class IIa, level of evidence B), but are rarely used in clinical practice. Analyses of the
pericardial uid specic gravity (>1015), protein level (>3.0 g/dL), uid/serum ratio

21

>0.5, LDH >200 mg/dL, serum/uid >0.6, and glucose can separate exudates from
transudates, but are not directly diagnostic (class IIb). Nevertheless, purulent effusions
with positive cultures have signicantly lower uid glucose levels than non infectious
effusions. White cell count is highest in inammatory and infectious diseases, and
lowest in myxedema. Technical advances in instrumentation, introduction of
pericardioscopy and contemporary pathology, virology, and molecular biology
techniques have improved the diagnostic value of epicardial/pericardial biopsy.
Pericardioscopy performed through air instead of uid, made it possible to inspect large
areas of pericardial surface, select the biopsy site, and take numerous samples. Targeted
pericardial/epicardial biopsy during pericardioscopy was particularly useful in the
diagnosis of neoplastic pericarditis. No major complications were reported with the use
of exible pericardioscopies. Suchtechniques and approaches are warranted in skilled
tertiary referral centres for selected cases, when a specic diagnosis, thatmay
requireatargeted therapy (i.e. neoplastic pericardial effusion), is suspected and cannot be
diagnosed by traditional diagnostic means.10
The diagnosis of autoreactive pericarditis is established using the following criteria: (i)
increased number of lymphocytes and mononuclear cells .5000/mm3 (autoreactive
lymphocytic), or the presence of anti- bodies against heart muscle tissue
(antisarcolemmal) in the pericar- dial uid (autoreactive antibody mediated); (ii) signs
of myocarditis on epicardial/endomyocardial biopsies by .14 cells/mm2; (iii) exclusion
of active viral infection both in pericardial effusion and endomyocardial/ epimyocardial
biopsies (no virus isolation, no IgM titer against cardiotropic viruses in pericardial
effusion, and negative PCR for major cardiotropic viruses); (iv) tuberculosis, Borrelia
burgdorferi, Chlamydia pneumoniae, and other bacterial infection excluded by PCR
and/or cultures; (v) neoplastic inltration absent in pericardial effusion and biopsy
samples; (vi) exclusion of systemic, metabolic disorders, and uraemia. This is
essentially a diagnosis of exclusion for pericardial effusions with an autoimmune
pathogenesis not related to a known systemic inammatory disease, and that may be
efciently treated by corticosteroids.10
The presence of elevated inammatory markers and other criteria for pericarditis (chest
pain, pericardial rubs, and ECG changes) suggests pericarditis and management should
follow the triage and management recommended for pericarditis.30 Integrated

22

cardiovascular imaging, including echocardiography, CT, and CMR may provide

valuable aid in the search for the cause of pericardial effusions. Although
echocardiography remains the primary diagnostic tool for the study of pericardial
diseases because of its widespread availability, portability, and limited costs, CT and
CMR provide a larger eld of view, allowing the detection of loculated pericardial
effusion, pericardial thickening and masses, as well as associated chest abnormalities.
Cardiac magnetic resonance may also provide a combined morphological and functional
evaluation. For both CT and CMR, the pericardium is ideal for imaging studies, because
of a high natural contrast between pericardial layers separated by pericardial uid, and
contiguous fat tissue in the mediastinal and subepicardial space. Computed tomography
density measurements and the analysis of CMR signals may enable the initial
characterization of pericardial uid better than echocardiography. With inamed
pericardium, the patient usually has the combination of effusion and pericardial
thickening. On CT, generally, pericardial effusions are of low density in the range of 0
20 Hounseld units (HU). When the effusion contains higher amounts of protein, such
as in bacterial infections, or when it is haemorrhagic, its density may rise to 50 HU and
more. Inamed pericardium may also show contrast enhancement. In CT imaging of the
pericardium, difculty may be encountered in differentiating uid from thickened
pericardial tissue. Cardiac magnetic resonance is superior to CT in differentiating uid,
especially highly proteinaceous exudative effusions, from thickened pericardium. On
the contrary, CT may detect even minimal amounts of pericardial calcium, whereas
CMR may miss signicant deposits. Computed tomography requires less time than
echocardiography and CMR. However, CT requires the use of intravenously
administered iodinated contrast materials and ionizing radiation. Moreover, if performed
without ECG gating, CT may lead to cardiac motion artefacts, that limit the evaluation
of pericardial thickness. However, the use of more recent and updated CT scanners with
a greater spatial and temporal resolution and more sophisticated algorithms for image
reconstruction may allow a signicant reduction in CT imaging artefacts. Cardiac
magnetic resonance has a superior ability to characterize pericardial effusions and
masses with the use of a combination of T1 weighted, T2-weighted, and gradientrecalled echo cine sequences without the use of either iodinated contrast material or
ionizing radiation. However, a possible disadvantage of CMR with ECG gating is that

23

arrhythmias, often associated with myopericardial diseases, may cause artefacts.

Another disadvantage of CMR is related to its limited availability and higher costs. Use
of i.v. injected gadolinium may be useful for pericarditis detection, because gadolinium
has been reported to enhance inamed pericardium, as well as for the detection of
concomitant myocardial involvement in myopericarditis.10

24

Figure Presentation of a mild (A) vs. moderate to large pericardial effusions (B) on
echocardiography. Mild pericardial effusion is evident adjacent to the right atrium in
four-chambers view and only posterior in parasternal long-axis view (A). As uid
accumulates, the effusion becomes circumferential (B). Pe, pericardial effusion; RA,
right atrium; Ao, aorta.10
TREATMENT
Symptoms and signs suggestive of pericardial involvement may be the presenting
clinical feature of either primary or secondary malignant cardiac disease, but they are
much more frequently present in patients under treatment for advanced malignancy. Life
expectancy is short as concomitant metastases are nearly always present elsewhere. In
these instances, adequate management of pericardial effusion may contribute to
palliation of the symptomsin a significant number of patientsand possibly to
prolonged survival (in an undefined number of cases). Although the main causes of
death in patients with malignancy are unrelated to cardiac involvement, in some
necropsy series pericardial metastases are commonly found, particularly in lung cancer
(35%) and breast cancer (25%) on the other hand, cardiac symptoms are mainly related
to the presence of tamponade, which is present in a significant number of patients,

25

although it has no negative impact on survival if it is correctly managed. In patients with

malignancy and pericardial effusion the first step is to determine whether the effusion is
secondary to neoplastic pericardial involvement or if it is an epiphenomenon
(non-malignant effusion) related to the management of the cancer (such as previous
thoracic irradiation) or effusions of unknown origin. In these two latter situations, an
invasive procedure may be warranted in the absence of tamponade as the diagnostic
yield of both pericardial fluid and tissue is high for malignancy. The management of
cardiac tamponade in patients with secondary neoplastic pericardial involvement has
two targetsrelief of symptoms, and prevention of recurrences. Pericardiocentesis
alleviates symptoms in most cases. It is a safe, simple, and widely available procedure
with few complications if it is done under echocardiographic guidance. Probably it is
the procedure of choice in end stage patients, when recurrence of effusion is not a real
issue. In patients surviving longer the pericardial fluid may re-accumulate, and isolated
pericardicentesis prevents this in only about 50% of cases. 11
In such patients a more aggressive approach with surgery may be warranted. Patient
management has to be individualized (type and stage of neoplasm, general condition,
etc) as even the best possible treatment for responsive types of tumour (for example,
lymphoma) with neoplastic pericardial involvement is associated with survival of only
about one year.11
The therapy of pericardial effusion should be targeted at the aetiology as much as
possible. In 60% of cases, the effusion is associated with a known disease, 18 and the
essential treatment is that of the underlying disease. When pericardial effusion is
associated with pericarditis, management should follow that of pericarditis.
Nevertheless, when diagnosis is still unclear or idiopathic, and inammatory markers
are elevated, a trial of aspirin or a nonsteroidal anti-inammatory drug (NSAID) can be
prescribed also to evaluate the response. A viral or idiopathic form is often responsive to
such empiric therapy. For the management of recurrent inammatory cases, the rst step
is considering the combination of aspirin or a NSAID plus colchicine, while
corticosteroids at low to moderate doses may be considered for specic indications (i.e.
systemic inammatory diseases and prenancy), and in case of intolerance,
contraindications, or failure of aspirin/NSAID; other therapies are based on less solid
evidence: less toxic and less expensive drugs (e.g. azathioprine or methotrexate) should

26

be preferred, tailoring the therapy for the individual patient and the physician
experience.
Ibuprofen is proposed as the favourite rst choice for empiric anti-inammatory
therapy of pericarditis, due to rare side effects, favourable effect on the coronary ow,
and the large dose range. However, other approaches have been published, and aspirin is
used as rst favourite choice in several clinical trials in the setting of acute and recurrent
pericarditis. For patients who already are taking or need aspirin, such drug is the best
anti inammatory choice. In the setting of post-myocardial infarction pericarditis,
ibuprofen, which increases the coronary ow, is the preferred agent of choice according.
Aspirin has been also successfully applied.10
Other nonsteroidal agents may increase the risk of thinning the infarction zone.
Corticosteroid therapy can be used for refractory symptoms only, but could delay
myocardial infarction healing (class IIa indication, level of evidence B). Post infarction
pericardial effusion >10 mm may be associated with haemopericardium, and up to twothirds of these patients may develop tamponade/free wall rupture. In this setting, urgent
surgical treatment is life saving. However, if the immediate surgery is not available or
contraindicated, pericardiocentesis, and intrapericardial brin glue instillation could
provide an alternative immediate treatment. In the setting of autoreactive pericardial
effusion, growing evidence supports the possible use of intrapericardial therapies to
reduce side effects related to the oral use of corticosteroids.10
When a pericardial effusion becomes symptomatic without evidence of inammation or
when empiric anti-inammatory drugs are not successful, drainage of the effusion
should be considered. Pericardiocentesis with prolonged pericardial drainage till 30
mL/24 h is recommended to promote adherence of pericardial layers and prevent further
accumulation of uid, although evidence to support this indication is based on case
reports, retrospective studies, and expert opinion. If pericardiocentesis is not feasible or
fails, the creation of a so called pericardial window should be considered either by
conventional heart surgery or videoassisted thoracoscopy. Balloon pericardiotomy is an
alternative to surgical creation of a pericardial window, which has been shown
successful especially in the setting of neoplastic pericardial disease. The technique
involves inserting a deated single catheter or double balloon catheters into the
pericardial space using a subxiphoid approach under uoroscopic or echocardiographic

27

guidance. Although successful in preventing recurrence in 80% of cases, stretching of

the pericardium is often painful so appropriate analgesia is recommended. A
recommendation to pericardiectomy for frequent and highly symptomatic recurrences
resistant to medical treatment. Other reported indications include repeated recurrences
with cardiac tamponade, and evidence of serious steroid toxicity. Although surgical
experiences are not always concordant, pericardiectomy is generally considered as a
therapeutic option of doubtful efcacy in recurrent idiopathic pericarditis or pericardial
effusion and should be considered only in ex- ceptional cases. Chronic permanent
constriction remains the major indication for such intervention. However, incessant
pericarditis, as distinguished from recurrent intermittent pericarditis, may respond
favourably to surgical removal, especially in the presence of recurrent pericardial
effusion. An idiopathic chronic pericardial effusion is dened as a collection of
pericardial uid that persists for 3 months and has no apparent cause; large effusions
have a risk of progression to cardiac tamponade (up to one third, according to a Spanish
study). On this basis some authors have advocated the need for pericardiectomy for such
cases, whenever a large effusion recurs after pericardiocentesis. Since drainage is
relatively safe and easy in some cases with guided pericardiocentesis, drainage has been
recommended for large subacute effusions, that do not respond to empiric therapy, and
are stable after several weeks (e.g. 68 weeks), especially when there are signs of right
sided collapse, in order to prevent the possible progression of the effusion towards
tamponade following additional events (e.g. pericarditis, bleeding following chest
trauma).12

28

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