Background

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. (See Etiology.)

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 (see the image below).
(See Presentation, Workup, Treatment, and Medication.)

This image is from a patient with malignant pericardial

effusion. Note the "water-bottle" appearance of the cardiac silhouette in the anteroposterior
(AP) chest film.

Embryology

In the human embryo, the pericardial cavity develops from the intraembryonic celom during
the fourth week. The pericardial cavity initially communicates with the pleural and peritoneal
cavities, but during normal development these are separated by the eighth week.

The visceral and parietal pericardium are derived from the mesoderm, albeit from different
parts of the embryo. The visceral pericardium develops from splanchnic mesoderm, as cells
originating from the sinus venous spread out over the myocardium. The parietal pericardium
derives from lateral mesoderm that covers and accompanies the developing pleuropericardial
membrane, which will eventually separate the pleural and pericardial cavities. In healthy
subjects, the pericardium covers the heart and great vessels, with the exception of only
partially covering the left atrium.

Congenital absence of the pericardium can occur and can be either partial or complete. This
condition is often clinically silent, but it can potentially lead to excessive cardiac motion (in
the case of complete absence), causing vague chest pain or dyspnea, or, in the case of partial
absence with significant defects, strangulation of heart muscle and possible death.[1]

Physiology

The pericardial space normally contains 15-50 mL of fluid, which serves as lubrication for
the visceral and parietal layers of the pericardium. This fluid is thought to originate from the
visceral pericardium and is essentially an ultrafiltrate of plasma. Total protein levels are
generally low; however, the concentration of albumin is increased in pericardial fluid owing
to its low molecular weight.

The pericardium and pericardial fluid provide important contributions to cardiac function,
including the following:

The parietal pericardium contributes to resting diastolic pressure, and is responsible

for most of this pressure in the right atrium and ventricle

Through their ability to evenly distribute force across the heart, the pericardial
structures assist in ensuring uniform contraction of the myocardium

The normal pericardium can stretch to accommodate a small amount of fluid without a
significant change in intrapericardial pressure, although once this pericardial reserve volume
is surpassed, the pressure-volume curve becomes steep. With slow increases in volume,
however, pericardial compliance can increase to lessen the increase in intrapericardial
pressure.

Pathophysiology
Clinical manifestations of pericardial effusion are highly dependent on the rate of
accumulation of fluid in the pericardial sac. Rapid accumulation of pericardial fluid may
cause elevated intrapericardial pressures with as little as 80 mL of fluid, while slowly
progressing effusions can grow to 2 L without symptoms.

Understanding the properties of the pericardium can help to predict changes within the heart
under physiologic stress.

By distributing forces across the heart, the pericardium plays a significant role in the
physiologic concept of ventricular interdependence, whereby changes in pressure, volume,
and function in one ventricle influence the function of the other.

The pericardium plays a pivotal role in cardiac changes during inspiration. Normally, as the
right atrium and ventricle fill during inspiration, the pericardium limits the ability of the left-
sided chambers to dilate. This contributes to the bowing of the atrial and ventricular septums
to the left, which reduces left ventricular (LV) filling volumes and leads to a drop in cardiac
output. As intrapericardial pressures rise, as occurs in the development of a pericardial
effusion, this effect becomes pronounced, which can lead to a clinically significant fall in
stroke volume and eventually progress to the development of pericardial tamponade.

The pericardium plays a beneficial role during hypervolemic states by limiting acute cardiac
cavitary dilatation.

Etiology
The cause of abnormal fluid production depends on the underlying etiology, but it is usually
secondary to injury or insult to the pericardium (ie, pericarditis). Transudative fluids result
from obstruction of fluid drainage, which occurs through lymphatic channels. Exudative
fluids occur secondary to inflammatory, infectious, malignant, or autoimmune processes
within the pericardium.

In up to 60% of cases, pericardial effusion is related to a known or suspected underlying

process. Therefore, the diagnostic approach should give strong consideration to coexisting
medical conditions.

Idiopathic

In many cases, the underlying cause is not identified. However, this often relates to the lack
of extensive diagnostic evaluation.

Infectious

Human immunodeficiency virus (HIV) infection can lead to pericardial effusion through
several mechanisms, including the following:

Secondary bacterial infection

Opportunistic infection

Malignancy (Kaposi sarcoma, lymphoma)

"Capillary leak" syndrome, which is associated with effusions in other body cavities

The most common cause of infectious pericarditis and myocarditis is viral. Common
etiologic organisms include coxsackievirus A and B, and hepatitis viruses. Other forms of
infectious pericarditis include the following:

Pyogenic - Pneumococci, streptococci, staphylococci, Neisseria, Legionella species

Tuberculous

Fungal - Histoplasmosis, coccidioidomycosis, Candida

Syphilitic

Protozoal

Parasitic

Neoplastic

Neoplastic disease can involve the pericardium through the following mechanisms:

Direct extension from mediastinal structures or the cardiac chamber

Retrograde extension from the lymphatic system

 Hematologic seeding

Malignancies with the highest prevalence of pericardial effusion include lung (37% of
malignant effusions) and breast (22%) malignancies, as well as leukemia/lymphoma (17%).
However, patients with malignant melanoma or mesothelioma also have a high prevalence of
associated pericardial effusions.

Postoperative/postprocedural

Pericardial effusions are common after cardiac surgery. In 122 consecutive patients studied
serially before and after cardiac surgery, effusions were present in 103 patients; most
appeared by postoperative day 2, reached their maximum size by postoperative day 10, and
usually resolved without sequelae within the first postoperative month.

In a retrospective survey of more than 4,500 postoperative patients, only 48 were found to
have moderate or large effusions by echocardiography; of those, 36 met diagnostic criteria for
tamponade. The use of preoperative anticoagulants, valve surgery, and female sex were
associated with a higher prevalence of tamponade.[2]

Symptoms and physical findings of significant postoperative pericardial effusions are

frequently nonspecific, and echocardiographic detection and echo-guided pericardiocentesis,
when necessary, are safe and effective; prolonged catheter drainage reduces the recurrence
rate.[3]

Pericardial effusions in cardiac transplant patients are associated with an increased prevalence
of acute rejection.[4]

Other

Less common causes of pericardial effusion include the following:

Uremia

Myxedema

Severe pulmonary hypertension

Radiation therapy

Acute myocardial infarction - Including the complication of free wall rupture

Aortic dissection - Leading to hemorrhagic effusion from leakage into the pericardial
sac

Trauma

Hyperlipidemia

Chylopericardium
 Familial Mediterranean fever

Whipple disease

Hypersensitivity or autoimmune related -Systemic lupus erythematosus,[5] rheumatoid

arthritis, ankylosing spondylitis, rheumatic fever, scleroderma, Wegener
granulomatosis

Drug associated - Eg, procainamide, hydralazine, isoniazid, minoxidil, phenytoin,

anticoagulants, methysergide

Epidemiology
Occurrence in the United States

Few large studies have characterized the epidemiology of pericardial effusion; however, the
available data consistently show that pericardial effusion is more prevalent than is clinically
evident. A higher incidence of it is associated with certain diseases.

Small pericardial effusions are often asymptomatic, and pericardial effusion has been found
in 3.4% of subjects in general autopsy studies.

A wide variety of malignant neoplasms and hematologic malignancies can lead to pericardial
effusion. Data on the prevalence varies, with some studies showing the presence of
pericardial effusion as high as 21% in such patients. A large study by Bussani et al showed
cardiac metastases (9.1%) and pericardial metastases (6.3%) in cases of death from all causes
in individuals with an underlying carcinoma at autopsy.[6] As previously mentioned,
malignancies with the highest prevalence of pericardial effusion include lung (37% of
malignant effusions) and breast (22%) malignancies, as well as leukemia/lymphoma (17%).

Patients with HIV, with or without acquired immunodeficiency syndrome (AIDS), are also
found to have an increased prevalence of pericardial effusion.[7] Studies have shown the
prevalence of pericardial effusion in these patients to range from 5-43%, depending on the
inclusion criteria, with 13% having moderate to severe effusion. The incidence of pericardial
effusion in patients infected with HIV has been estimated at 11%; however, it appears that
highly active antiretroviral therapy (HAART) may have reduced the incidence of HIV-
associated effusions.[8]

Race- and age-related demographics

No consistent difference among races is reported in the literature. AIDS patients with
pericardial effusion are more likely to be white.

Pericardial effusion is observed in all age groups. The mean occurrence is in the fourth or
fifth decades, although it is earlier than this in patients with HIV.[7]

Prognosis
Most patients with acute pericarditis recover without sequelae. Predictors of a worse outcome
include the following:

Fever greater than 38C

Symptoms developing over several weeks in association with immunosuppressed

state

Traumatic pericarditis

Pericarditis in a patient receiving oral anticoagulants

A large pericardial effusion (>20 mm echo-free space or evidence of tamponade)

Failure to respond to nonsteroidal anti-inflammatory drugs (NSAIDs)

In a series of 300 patients with acute pericarditis, 254 (85%) did not have any of the high-risk
characteristics and had no serious complications. Of these low-risk patients, 221 (87%) were
managed as outpatients and the other 13% were hospitalized when they did not respond to
aspirin.

Patients with symptomatic pericardial effusions from HIV/AIDS or cancer have high short-
term mortality rates.

Morbidity and mortality

The morbidity and mortality of pericardial effusion is dependent on etiology and comorbid
conditions. Idiopathic effusions are well tolerated in most patients. As many as 50% of
patients with large, chronic effusions (effusions lasting longer than 6 months) have been
found to be asymptomatic during long-term follow-up.

Pericardial effusion is the primary or contributory cause of death in 86% of cancer patients
with symptomatic effusions. The survival rate for patients with HIV and symptomatic
pericardial effusion is 36% at 6 months and 19% at 1 year.

Pericardial tamponade

Pericardial tamponade, which is heralded by the equalization of diastolic filling pressures,

can lead to severe hemodynamic compromise and death. It is treated with expansion of
intravascular volume (small amounts of crystalloids or colloids may lead to improvement,
especially in hypovolemic patients) and urgent pericardial drainage. Positive-pressure
ventilation should be avoided, if possible, as this decreases venous return and cardiac output.
Vasopressor agents are of little clinical benefit.

Proceed to Clinical Presentation

History
Cardiovascular symptoms in pericardial effusion can include the following:

Chest pain, pressure, discomfort - Characteristically, pericardial pain may be relieved

by sitting up and leaning forward and is intensified by lying supine.

Light-headedness, syncope

Palpitations

Respiratory symptoms can include the following:

Cough

Dyspnea

Hoarseness

Neurologic symptoms of pericardial effusion can include anxiety and confusion, while
hiccoughs may occur as a gastrointestinal (GI) symptom.

Physical Examination
Cardiovascular findings in pericardial effusion can include the following:

Classic Beck triad of pericardial tamponade - Hypotension, muffled heart sounds,

jugular venous distention

Pulsus paradoxus - Exaggeration of physiologic respiratory variation in systemic

blood pressure, defined as a decrease in systolic blood pressure of more than 10mm
Hg with inspiration, signaling falling cardiac output during inspiration

Pericardial friction rub

Tachycardia

Hepatojugular reflux - This can be observed by applying pressure to the periumbilical

region; a rise in the jugular venous pressure (JVP) of greater than 3 cm H2 O for more
than 30 seconds suggests elevated central venous pressure (however, transient
elevation in JVP may be normal)

Pericardial friction rub, the most important physical sign of acute pericarditis, may have up to
3 components per cardiac cycle and is high-pitched, scratching, and grating. It can sometimes
be elicited only when firm pressure with the diaphragm of the stethoscope is applied to the
chest wall at the left lower sternal border. The pericardial friction rub is heard most frequently
during expiration with the patient upright and leaning forward.

Respiratory findings can include the following:

Tachypnea
 Decreased breath sounds - Secondary to pleural effusions[9]

Ewart sign - Dullness to percussion beneath the angle of left scapula from
compression of the left lung by pericardial fluid

Hepatosplenomegaly represents a GI symptom of pericardial effusion. Findings in the

patients extremities can include weakened peripheral pulses, edema, and cyanosis.

Proceed to Differential Diagnoses

Differential Diagnoses
Cardiac Tamponade

Cardiomyopathy, Dilated

Myocardial Infarction

Pericarditis, Acute

Pericarditis, Constrictive

Pericarditis, Constrictive-Effusive

Pericarditis, Uremic

Pulmonary Edema, Cardiogenic

Pulmonary Embolism

Proceed to Workup

Approach Considerations
The extent to which pericardial effusions should be evaluated with fluid analysis remains an
area of some debate. Initially, in a patient with a new pericardial effusion, the likelihood of
myocarditis or pericarditis should be assessed, and the initial diagnostic evaluation should be
directed toward these conditions.

In general, all patients with pericardial tamponade, suspected purulent effusion, or poor
prognostic indicators in the setting of pericarditis should undergo diagnostic
pericardiocentesis. Those with recurrent effusions or large effusions that do not resolve with
treatment of the underlying condition may also warrant fluid analysis.

Electrocardiographic (ECG) changes are part of the criteria for diagnosing acute pericarditis,
and therefore an ECG should be performed at the outset of the evaluation.[10]
Echocardiography is the imaging modality of choice for the diagnosis of pericardial effusion,
as the test can be performed rapidly and in unstable patients.

Lab Studies
The following lab studies may be performed in patients with suspected pericardial effusion:

Electrolytes - To assess for metabolic abnormalities (eg, renal failure)

Complete blood count (CBC) with differential - Leukocytosis for evidence of

infection, as well as cytopenias, as signs of underlying chronic disease (eg, cancer,
HIV)

Cardiac biomarkers

Other markers of inflammation, such as erythrocyte sedimentation rate and C-

Reactive protein - While these do not aid in identifying specifics, they can be used to
potentially assess the need for anti-inflammatory agents (ie, corticosteroids,
colchicine, NSAIDs), especially in the setting of recurrent effusions.[11]

Thyroid-stimulating hormone - Thyroid-stimulating hormone screen for

hypothyroidism

Blood cultures in the presence of systemic inflammatory response syndrome (SIRS)

or fever; in general, specific viral studies are low yield and therefore not
recommended[12]

Rheumatoid factor, immunoglobulin complexes, antinuclear antibody test (ANA), and

complement levels (which would be diminished) - In suspected rheumatologic causes

Specific infectious disease testing, based upon clinical suspicion, such as (1)
tuberculin skin testing or QuantiFERON-TB assay; (2) rickettsial antibodies if there is
a high index of suspicion for tick-borne disease; and HIV serology

Cardiac enzymes

The troponin level is frequently minimally elevated in acute pericarditis, usually in the
absence of an elevated total creatine kinase level. Presumably, this is due to some
involvement of the epicardium by the inflammatory process.

Although the elevated troponin may lead to the misdiagnosis of acute pericarditis as a
myocardial infarction, most patients with an elevated troponin and acute pericarditis do not
have findings at angiography consistent with acute coronary syndrome. An elevated troponin
level in acute pericarditis typically returns to normal within 1-2 weeks and is not associated
with a worse prognosis.

Pericardial fluid analysis

It should be noted that routine biochemical and cell-count analysis has a low yield in
diagnosing the cause of effusion.[13] In contrast, Gram stain and culture can ascertain the
etiology convincingly. It is routine for the following tests to be considered part of the
standard pericardial fluid analysis:

Lactic (acid) dehydrogenase (LDH), total protein - The Light criteria (for exudative
pleural effusion) found to be as reliable in distinguishing between exudative and
transudative effusions: (1) total protein fluid-to-serum ratio >0.5, (2) LDH fluid-to-
serum ratio >0.6, (3) LDH fluid level exceeds two thirds of upper limit of normal
serum level[14]

Other indicators suggestive of exudate - Specific gravity >1.015, total protein >3.0
mg/dL, LDH >300 U/dL, glucose fluid-to-serum ratio < 1

Cell count - Elevated leukocytes (ie, >10,000) with neutrophil predominance suggests
bacterial or rheumatic cause, although unreliable

Gram stain - Specific (but insensitive) indicator of bacterial infection

Cultures - Signal and identify infectious etiology

Fluid hematocrit for bloody aspirates - Hemorrhagic fluid hematocrits are usually
significantly less than simultaneous peripheral blood hematocrits

Cytology of pericardial fluid to assess for the presence of malignant cells

Special tests

These studies of the pericardial fluid should be considered individually based on the pretest
probability of the suspected coexisting condition. They include the following:

Viral cultures

Adenosine deaminase; polymerase chain reaction (PCR); culture for tuberculosis;

smear for acid-fast bacilli in suspected tuberculosis infection, especially in patients
with HIV

A definite diagnosis of tuberculous pericarditis is based on the demonstration of tubercle

bacilli in pericardial fluid or on a histologic section of the pericardium.

Probable tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a patient

with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with elevated
adenosine deaminase levels, and/or appropriate response to a trial of antituberculosis
chemotherapy.

Elevated carcinoembryonic antigen (CEA) levels in pericardial fluid have a high specificity
for malignant effusion.
Perform pericardial biopsy, especially if malignant pericardial effusion is suspected.[14] This
can be more diagnostic when combined with pericardioscopy.[15]

Chest Radiography
Findings in chest radiography include an enlarged cardiac silhouette (so-called water-bottle
heart) and a pericardial fat stripe. One third of patients have a coexisting pleural effusion.
Radiography is unreliable in establishing or refuting a diagnosis of pericardial effusion. (See
the image below.)

This image is from a patient with malignant pericardial

effusion. Note the "water-bottle" appearance of the cardiac silhouette in the anteroposterior
(AP) chest film.

Echocardiography
Echocardiography is the imaging modality of choice for the diagnosis of pericardial effusion,
as the test can be performed rapidly and in unstable patients. Most importantly, the
contribution of pericardial effusion to overall cardiac enlargement and the relative roles of
tamponade and myocardial dysfunction in altered hemodynamics can be evaluated with
echocardiography. (See the images below.)[16]

Echocardiogram (parasternal, long axis) of a patient with a

moderate pericardial effusion. Subcostal view of an

echocardiogram that shows a moderate to large amount of pericardial effusion.
 This echocardiogram shows a large amount of pericardial
effusion (identified by the white arrows).

Patients with viral cardiomyopathy, especially in the acute setting, may have a similar
presentation to patients with pericardial effusion, with an enlarged heart being seen on chest
radiographs. Echocardiography readily distinguishes the difference between enlarged cardiac
chambers and a pericardial effusion.

Two-dimensional echocardiography

Pericardial effusion appears as an echo-free space between the visceral and parietal
pericardium. Early effusions tend to accumulate posteriorly owing to expandable
posterior/lateral pericardium.

Large effusions are characterized by excessive motion within the pericardial sac, also called
swinging. Small effusions have an echo-free space of less than 10 mm and are generally seen
posteriorly. Moderate-sized effusions range from 10-20 mm and are circumferential. An echo-
free space of more than 20 mm indicates a large effusion. Fluid adjacent to the right atrium is
an early sign of pericardial effusion. (See the image below.)[17]

This image is from a patient with malignant pericardial

effusion. The effusion is seen as an echo-free region to the right of the left ventricle (LV).

Echocardiography may identify features that suggest hemodynamically significant cardiac

tamponade; however, this is, in fact a clincial not echocardiographic, diagnosis. These
findings include the following:

Collapse of the right atrium, especially if it lasts for a third of the cardiac cycle

Diastolic collapse of the right ventricle

In hypovolemic patients, the left atrium and left ventricle may also show signs of
collapse

Rarely, the cause of the effusion can also be ascertained from echocardiography. The
following echocardiographic findings may be helpful:
 Presence of a coagulum in the pericardial space indicating a bloody pericardial
effusion (aortic dissection, postoperative, or after other catheter-based procedures)

Presence of a pacemaker lead either in the vicinity or inside an area of localized

effusion, indicating lead perforation as a cause

Presence of tumor (primary or secondary) in the pericardial space

M-mode echocardiography

M-mode echocardiography is adjunctive to two-dimensional (2-D) imaging for the detection

of pericardial effusion. Effusions can be classified using M-mode according to the following
system proposed by Horowitz et al[18] :

Type A - No effusion

Type B - Separation of epicardium and pericardium

Type C1 - Systolic and diastolic separation of pericardium

Type C2 - Systolic and diastolic separation of pericardium, attenuated pericardial

motion

Type D - Pronounced separation of pericardium and epicardium with large echo-free

space

In the parasternal long-axis and apical 4-chamber views, discordant changes in right and left
ventricular cavity size can suggest pronounced interventricular dependence, also suggesting
an echocardiographic substrate for tamponade. It is important to note that these changes
occur independent of the cardiac cycle (as these are dependent on respiration).

Doppler echocardiography

Transmitral and transtricuspid inflow velocities should be investigated to assess for

respiratory variation. Decreases in flow during inspiration (transmitral >25%) or expiration
(transtricuspid >40%) should raise the suspicion of clinically significant interventricular
dependence and tamponade physiology. However, these findings may be less evident or, in
fact, absent in patients on mechanical ventilation, even in the presence of a hemodynamically
significant pericardial effusion.[19]

Pulmonic vein inflow may show a decrease in early diastolic flow with hemodynamically
significant effusions. Plethoric inferior vena cava with less than 50% collapse during
inspiration may indicate elevated right atrial pressures. Hepatic vein diastolic flow reversal
seen during expiration is another classic manifestation of ventricular interdependence.

Transesophageal echocardiography

Localized compressive masses, such as postoperative mediastinal hematoma, can cause

tamponade without any of the classic 2-dimensional or Doppler manifestations.
Transesophageal echocardiography maintains all of the advantages of transthoracic
echocardiography and is useful in characterizing loculated effusions. However, this imaging
study may be difficult to perform in patients with symptomatic effusions due to
hemodynamic instability, with the required sedation being more difficult.

Intracardiac echocardiography

Intracardiac echocardiography (ICE) is generally reserved for the assessment of pericardial

effusion in the setting of a percutaneous interventional or electrophysiologic procedure.
Phased-array ICE systems can perform 2-D and Doppler interrogations.

False-positive findings

False-positive echocardiographic findings can occur in the presence of pleural effusions,

pericardial thickening, increased epicardial fat tissue, atelectasis, and mediastinal lesions.
Pericardial cysts, which are usually benign, can be seen classically in the right cardiophrenic
angle and can be confused with pericardial effusion.

Epicardial fat tissue is more prominent anteriorly but may appear circumferentially, thus
mimicking effusion. Fat is slightly echogenic and tends to move in concert with the heart, 2
characteristics that help to distinguish it from an effusion, which is generally echolucent and
motionless.[16, 20, 21]

In patients with pericardial effusion, imaging from low to midposterior thorax can provide
additional diagnostic echocardiographic images and should be used in patients in whom
conventional images are technically difficult or require additional information.

CT Scanning and MRI

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) may be
superior to echocardiography in detecting loculated pericardial effusions, especially when
these are located anteriorly. Also, these modalities allow for greater visualization of the
thoracic cavity and adjacent structures and therefore may identify abnormalities relating to
the cause of the effusion.

CT scanning

CT scanning can potentially determine the composition of fluid and may detect as little as
50mL of fluid. This modality can also detect pericardial calcifications, which can be
indicative of constrictive pericarditis.

CT scanning results in fewer false-positive findings than echocardiography. However, it can

be problematic in patients who are unstable, given the amount of time required to transport
them to and from the scanner and to perform the test.

Certain classic CT signs of tamponade have also been described, such as dilated venae cavae,
reflux of contrast into the azygos vein and inferior vena cava, deformity or compression of
the cardiac chambers, and bowing of the interventricular septum.[22]
MRI

MRI can detect as little as 30 mL of pericardial fluid. It may be able to distinguish

hemorrhagic and nonhemorrhagic fluids, as hemorrhagic fluids have a high signal intensity
on T-1 weighted images, whereas nonhemorrhagic fluids have a low signal intensity.
Nodularity or irregularity of the pericardium seen on MRI may be indicative of a malignant
effusion.

MRI is more difficult to perform acutely than CT scanning is, given the length of time the
patient must remain in the scanner.

Late gadolinium enhancement can reveal areas of inflammation, which can potentially help
decide about anti-inflammatory therapy in recurrent pericarditis and can also aid in the
diagnosis of effusive-constrictive pericarditis.[23]

Electrocardiography
Early in the course of acute pericarditis, the ECG typically displays diffuse ST elevation in
association with PR depression (see the image below). The ST elevation is usually present in
all leads except for aVR, although in postmyocardial infarction pericarditis, the changes may
be more localized. (Patients with uremic pericarditis frequently do not have the typical
electrocardiographic abnormalities.)

This electrocardiogram (ECG) is from a patient with

malignant pericardial effusion. The ECG shows diffuse low voltage, with a suggestion of
electrical alternans in the precordial leads.

Classically, the electrocardiographic changes of acute pericarditis evolve through 4

progressive stages, as follows:

Stage I - Diffuse ST-segment elevation and PR-segment depression

Stage II - Normalization of the ST and PR segments

Stage III - Widespread T-wave inversions: This is important to differentiate from

myocardial infarction as T-wave inversions in pericarditis usually occur after ST-
segment normalization, unlike myocardial infarction

Stage IV - Normalization of the T waves

Electrical alternans, which is the beat-to-beat variation in the direction and amplitude of the
QRS complex, is the electrical signature of swinging of the heart in the pericardial fluid. In
extreme cases, it can involve the P as well as the T waves. It is specific, but not sensitive, for
tamponade and can also be seen in large pericardial effusions.[24]
Low-voltage QRS complexes, classically defined as total amplitude of the QRS complex less
than 0.5 mv in the limb leads and less than 1 mv in the precordial leads, can also be seen in
large effusions and tamponade. One study using limb lead criteria showed that it is more
specific for tamponade rather than an effusion.[25]

Pericardiocentesis and Pericardioscopy

Pericardiocentesis

This procedure is used for diagnostic as well as therapeutic purposes. Support for the use of
echocardiographic guidance is increasing, unless emergent treatment is required. Indications
for pericardiocentesis include impending hemodynamic compromise (ie, pericardial
tamponade), suspected infectious or neoplastic etiology, and uncertain etiology.

Pericardioscopy

This procedure is not universally available. It may increase diagnostic sensitivity in cases of
unexplained pericardial effusions, especially for neoplastic disease. It allows for visualization
of pericardium and for pericardial biopsies.

Proceed to Treatment & Manageme

Approach Considerations
Pharmacotherapy for pericardial effusion includes use of the following agents, depending on
etiology:

Aspirin/NSAIDs

Colchicine

Steroids

Antibiotics

Antineoplastic therapy (eg, systemic chemotherapy, radiation) in conjunction with

pericardiocentesis has been shown to be effective in reducing recurrences of malignant
effusions. Corticosteroids and NSAIDs are helpful in patients with autoimmune conditions.

Pericardial sclerosis

Several pericardial sclerosing agents have been used with varying success rates (eg,
tetracycline, doxycycline, cisplatin, 5-fluorouracil). The pericardial catheter may be left in
place for repeat instillation if necessary until the effusion resolves.

Complications include intense pain, atrial dysrhythmias, fever, and infection. Success rates
are reported to be as high as 91% at 30 days.
Surgery

Surgical treatments for pericardial effusion include the following:

Pericardiostomy

Pericardotomy

Thoracotomy

Sternotomy

Pericardiocentesis

Inpatient care

Patients with pericardial effusion who present with significant symptoms or cardiac
tamponade require emergent treatment and admission to the intensive care unit (ICU). The
pericardial catheter (if placed) should be removed within 24-48 hours to avoid infection.
Symptomatic patients should remain hospitalized until definitive treatment is accomplished
and/or symptoms have resolved

Outpatient care

Patients should be educated with regard to symptoms of increasing pericardial effusion and
should be evaluated whenever these symptoms begin to occur. Indications for
echocardiography after diagnosis include the following:

A follow-up imaging study to evaluate for recurrence/constriction - Repeat studies

may be performed to answer specific clinical questions.

The presence of large or rapidly accumulating effusions - To detect early signs of

tamponade

Transfer

Symptomatic patients requiring treatment (who are surgical candidates) should receive care at
an institution with cardiothoracic surgery capabilities.

Consultations

A cardiologist should be involved in the care of patients with pericardial effusion.

Cardiothoracic surgery may be required for recurrent or complicated cases.

Aspirin/NSAIDs
Most acute idiopathic or viral pericarditis occurrences are self-limited and respond to
treatment with aspirin (650 mg q6h) or another NSAID. For idiopathic or viral pericarditis,
ibuprofen is preferred, given its low adverse effect profile, favorable impact on the coronary
blood flow, and large dose range. Based on severity and response, the dose can range from
300-800 mg every 6-8 hours.[26]

Aspirin may be the preferred nonsteroidal agent to treat pericarditis after myocardial
infarction because other NSAIDs may interfere with myocardial healing. Indomethacin
should be avoided in patients who may have coronary artery disease.

In a study of 196 patients at high risk for tamponade because of pericardial effusion more
than 7 days after cardiac surgery, Meurin et al found that diclofenac was not effective in
reducing the size of the effusion or in preventing late cardiac tamponade. In the multicenter,
randomized, double-blind trial, patients received either diclofenac (50 mg) or placebo twice
daily for 14 days.[27]

Colchicine
The routine use of colchicine in combination with conventional therapy is supported by
results from the COlchicine for acute PEricarditis (COPE) trial. In this study, 120 patients
with a first episode of acute pericarditis (idiopathic, acute, postpericardiotomy syndrome, or
connective tissue disease) entered a randomized, open-label trial comparing aspirin treatment
alone with aspirin plus colchicine (1-2 mg for the first day followed by 0.5-1 mg daily for 3
mo).[28]

In the study, colchicine reduced symptoms at 72 hours (11.7% vs 36.7) and reduced
recurrence at 18 months (10.7% vs 36.7%). Colchicine was discontinued in 5 patients
because of diarrhea, but no other adverse events were noted. Importantly, none of the 120
patients developed cardiac tamponade or progressed to pericardial constriction. The ICAP
Trial (Investigation on Colchicine for Acute Pericarditis) will provide further information
regarding the use of colchicine as first-line therapy.[29]

Steroids
Steroid administration early in the course of acute pericarditis appears to be associated with
an increased incidence of relapse after the steroids are tapered. In the COPE trial, steroid use
was an independent risk factor for recurrence. Also, an observational study strongly
suggested that the use of steroids increases the probability of relapse in patients treated with
colchicine.[28]

Systemic steroids should be considered only in patients with recurrent pericarditis that is
unresponsive to NSAIDs and colchicine or as needed for treatment of an underlying
inflammatory disease. If steroids are to be used, an effective dose (1-1.5 mg/kg of
prednisone) should be given, and it should be continued for at least 1 month before slow
tapering. The European Society of Cardiology recommends that systemic corticosteroid
therapy be restricted to connective-tissue diseases, autoreactive pericarditis, or uremic
pericarditis.[26]

The intrapericardial administration of steroids has been reported to be effective in acute

pericarditis without producing the frequent reoccurrence of pericarditis that complicates the
use of systemic steroids,[30] but the invasive nature of this procedure limits its use.
Antibiotics
Purulent pericarditis

In patients with purulent pericarditis, urgent pericardial drainage combined with intravenous
(IV) antibacterial therapy (eg, vancomycin 1 g bid, ceftriaxone 1-2 g bid, and ciprofloxacin
400 mg daily) is mandatory. Irrigation with urokinase or streptokinase, using large catheters,
may liquify the purulent exudate, but open surgical drainage is preferable.

Tuberculous pericarditis

The initial treatment of tuberculous pericarditis should include isoniazid 300 mg daily,
rifampin 600 mg daily, pyrazinamide 15-30 mg/kg daily, and ethambutol 15-25 mg/kg daily.
Prednisone 1-2 mg/kg daily is given for 5-7 days and progressively reduced to
discontinuation in 6-8 weeks. Drug sensitivity testing is essential. Uncertainty remains
whether adjunctive corticosteroids are effective in reducing mortality or progression to
constriction.

Surgical resection of the pericardium remains the appropriate treatment for constrictive
pericarditis. The timing of surgical intervention is controversial, but many experts
recommend a trial of medical therapy for noncalcific pericardial constriction and
pericardiectomy in nonresponders after 4-8 weeks of antituberculosis chemotherapy.

Hemodynamic Support
Patients who have an effusion with actual or threatened tamponade should be considered to
have a true or potential emergency. Most patients require pericardiocentesis to treat or
prevent tamponade. However, treatment should be carefully individualized.

Hemodynamic monitoring with a balloon flotation pulmonary artery catheter is useful,

especially in patients with tamponade or threatened tamponade in whom a decision is made to
defer pericardiocentesis. Hemodynamic monitoring is also helpful after pericardiocentesis to
assess reaccumulation and the presence of underlying constrictive disease. However,
insertion of a pulmonary artery catheter should not be allowed to delay definitive therapy in
critically ill patients.

IV fluid resuscitation may be helpful in cases of hemodynamic compromise. In patients with

tamponade who are critically ill, IV positive inotropes (dobutamine, dopamine) can be used
but are of limited use and should not be allowed to substitute for or delay pericardiocentesis.

Pericardiocentesis
As previously mentioned, pericardiocentesis is used for diagnostic as well as therapeutic
purposes. Pericardial fluid drainage can be performed by percutaneous catheter drainage or
open surgical approach. Individual patient characteristics (eg, loculated vs circumferential,
recurrent pericardial effusion, need for pericardial biopsy and location of pericardial effusion)
and local practice patterns aid in deciding the optimal method of drainage.
Percutaneous pericardial fluid drainage (pericardiocentesis) is the most common method used
for pericardial fluid removal. It can be performed under fluoroscopic, echocardiographic, or
CT guidance.

Echocardiographic pericardial fluid drainage has established itself as the criterion standard
technique. In study of 1127 procedures performed on 977 patients, echocardiographic-guided
pericardiocentesis was successful in 97%, with 1.2% major and 3.5% minor complications.[31]
It also established the extended drainage as a means to reduce the recurrence rate.

Use of a needle that is at least 5cm long and 16-gauge in diameter and that has a short bevel
can minimize the risk of complications and should allow for adequate pericardial drainage. A
system allowing placement of a catheter over the needle is preferred.

Contrast echocardiography using agitated saline is useful in cases in which bloody fluid is
aspirated, to determine if the needle is in the ventricular cavity.

Attaching an ECG electrode to the pericardiocentesis needle is also useful for avoiding
myocardial puncture. Electrical activity will be seen on the monitor when the needle comes
into contact with atrial or ventricular myocardium. These changes may be delayed, however,
and instill a false sense of security in needle placement. Sense of touch and the findings on
aspiration should guide the procedure, with the clinician ultimately relying on good clinical
sense.

Complications of pericardiocentesis include ventricular rupture, dysrhythmias,

pneumothorax, myocardial and/or coronary artery laceration, and infection. Recurrence rates
for pericardial effusion within 90 days may be as high as 90% in patients with cancer.

Pericardiotomy and Pericardiostomy

Balloon pericardotomy

In this procedure, a catheter is placed in the pericardial space under fluoroscopy. Inflation of
the balloon creates a channel for passage of fluid into the pleural space, where reabsorption
occurs more readily. Balloon pericardiotomy may be useful for recurrent effusions.

CT-guided pericardiostomy

Patients with effusions after cardiothoracic surgery often have limited echocardiographic
windows, as well as loculated effusions, and may be on continued ventilatory support, all of
which increase the difficulty of echo-guided pericardiocentesis.

CT pericardial fluid drainage has evolved as an emerging technique suited to overcome this
dilemma. It has been shown as an alternative technique in patients in whom fluoroscopically
or echocardiographically guided pericardiocentesis is difficult. Echocardiography can be
limited due to various patient characteristics (eg, postoperative state, obesity, or chronic
obstructive pulmonary disease) or due to a limitation of echocardiography in differentiating
pericardial fluid from other possible surrounding structures.
In one large series, CT-directed diagnostic and therapeutic pericardiocentesis was attempted
in 261 patients, with 98.4% success, 0.3% major complications and 6.9% minor
complications.[32]

In 2010, Eichler et al reported their data on CT-guided pericardiocentesis in 20 patients who

were poor candidates for echocardiographic drainage or pericardial fluid was not well
visualized by echocardiography. All patients had successful drainage, with 0% mortality and
no major complications.[33]

A report by Palmer et al suggested that, in postsurgical cases, CT-guided pericardial drainage

is both safe and cost effective. The authors reported on 36 patients33 of whom underwent
major cardiothoracic surgery and 3 of whom were treated with minimally invasive procedures
whose symptomatic pericardial effusions were drained using CT-guided percutaneous
placement of an indwelling pericardial catheter.[34]

There were no clinically significant complications associated with any of the placement
procedures. Thirty-three patients experienced no symptom recurrence following catheter
removal, although pericardial effusion did recur in the remaining 3 patients, requiring a repeat
treatment.

Comparing procedure costs, the authors determined that the CT-guided tube
pericardiostomies cost 89% less than intraoperative pericardial window procedures would
have. No significant procedure-cost differences were found between CT-guided and
ultrasonographically guided tube pericardiostomies.

Subxiphoid Pericardial Window With Pericardiostomy

This procedure is associated with low morbidity, mortality, and recurrence rates, and can be
considered as a reasonable alternative diagnostic or treatment modality to pericardiocentesis
in selected patients.[35]

The surgery can be performed under local anesthesia. This is advantageous because general
anesthesia often leads to decreased sympathetic tone, resulting in hemodynamic collapse in
patients with pericardial tamponade and shock. This procedure may be less effective when
effusion is loculated.

One study indicated that the procedure may be safer and more effective at reducing
recurrence rates than pericardiocentesis. However, only patients who were hemodynamically
unstable underwent pericardiocentesis, and no change in overall survival rate was observed.

Thoracotomy and Median Sternotomy

Thoracotomy

This procedure should be reserved for patients in whom conservative approaches have failed.
Thoracotomy allows for creation of a pleuropericardial window, which provides greater
visualization of the pericardium. Thoracotomy requires general anesthesia and thus has
higher morbidity and mortality rates than does the subxiphoid approach.
Median sternotomy

This procedure is reserved for patients with constrictive pericarditis. The operative mortality
rate is high (5-15%).

Video-Assisted Thoracic Surgery

Video-assisted thoracic surgery (VATS) allows resection of a wider area of the pericardium
than the subxiphoid approach does, without the morbidity of thoracotomy.[36] The surgeon is
able to create a pleuropericardial window and address concomitant pleural pathology, which
is especially common in patients with malignant effusions.

One disadvantage of VATS is that it requires general anesthesia with single lung ventilation,
which may be difficult in otherwise seriously ill patients.

Proceed to Medication

Medication Summary
Most acute idiopathic or viral pericarditis occurrences are self-limited and respond to
treatment with an NSAID. The corticosteroid prednisone may be administered for severe
inflammatory pericardial effusions or when NSAID treatment has failed.

Research indicates that the anti-inflammatory drug colchicine, when used in combination
with conventional therapy, is more effective at reducing the symptoms and recurrence of
pericarditis than is conventional therapy alone.[28]

Autoimmune pericardial effusions may respond to treatment with anti-inflammatory

medications. In general, selection of an agent depends on the severity of the patient's
symptoms and the tolerability and adverse effect profiles of the medications.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Class Summary

These agents are used mostly for patients with active, nonhemorrhagic pericarditis with or
without pericardial effusion. NSAIDS have analgesic, anti-inflammatory, and antipyretic
activities.

The mechanism of action in pericarditis is not known, but NSAIDS may inhibit cyclo-
oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as
inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity,
neutrophil aggregation, and various cell-membrane functions.

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Indomethacin (Indocin)
Indomethacin is the drug of choice in this class, although other NSAIDs (ie, ibuprofen,
naproxen, aspirin) possess some efficacy. It is used as initial therapy for mild to moderately
severe inflammatory pericardial effusions.

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Ibuprofen (Advil, Motrin, Addaprin, Ultraprin)

Ibuprofen is a propionic acid derivative that reduces the formation of inflammatory mediators
by enzyme inhibition.

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Naproxen (Aleve, Anaprox, Naprosyn, Naprelan)

Naproxen is a propionic acid derivative that reduces the formation of inflammatory mediators
by enzyme inhibition.

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Diclofenac sodium (Cataflam, Voltaren SR, Zipsor)

Diclofenac possesses properties similar to those of the propionic acid derivatives and reduces
the formation of inflammatory mediators by enzyme inhibition. The tablets are immediate-
release formulations.

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Ketoprofen

Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are
indicated initially in small patients, elderly patients, and patients with renal or liver disease.
Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with
caution, and closely observe the patient's response.

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Aspirin (Bayer Aspirin, Ascriptin, Bufferin, Ecotrin)

Aspirin inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating
thromboxane A2.

Corticosteroids
Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic
effects. These agents modify the body's immune response to diverse stimuli.

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Prednisone

Prednisone is used for patients with severe inflammatory pericardial effusions or for those in
whom initial treatment with NSAIDs has failed. Other agents may be used if the adverse
effect profile warrants; dosages should be determined by prednisone equivalents.

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Methylprednisolone (Solu-Medrol, Depo-Medrol, A-Methapred)

Methylprednisolone is available in IV/IM and oral form. It decreases inflammation by

suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary
permeability. It is used for patients with severe inflammatory pericardial effusions or for
those in whom initial treatment with NSAIDs has failed.

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Prednisolone (Pediapred, Prelone, Orapred, Millipred)

Prednisolone is available in IV/IM and oral form. It decreases inflammation by suppressing

the migration of polymorphonuclear leukocytes and reversing increased capillary
permeability. It is used for patients with severe inflammatory pericardial effusions or for
those in whom initial treatment with NSAIDs has failed.

Anti-inflammatory Agents
Class Summary
These agents inhibit key factors involved in inflammatory reactions.

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Colchicine

Colchicine is an alkaloid extract that inhibits microtubule formation and has unique anti-
inflammatory properties. The drug concentrates well in leukocytes and reduces neutrophilic
chemotaxis and motility. Colchicine reduces the release of lactic acid and proinflammatory
enzymes. It inhibits the release of histamine-containing granules from mast cells, which may
be important in the pathogenesis of elastic tissue changes found in anetoderma.

The use of colchicine in autoimmune disease is primarily empiric, and the mechanism of
action in the reduction of inflammation is not clear. Colchicine is not truly an
immunomodulating agent.