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. [11]
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:
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Electrolytes - To assess for metabolic abnormalities (eg, renal failure)
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Complete blood count (CBC) with differential - Leukocytosis for evidence of infection, as well as cytopenias, as signs of underlying chronic disease (eg, cancer, HIV)
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Cardiac biomarkers
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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. [12]
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Thyroid-stimulating hormone - Thyroid-stimulating hormone screen for hypothyroidism [13]
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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 [14]
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Rheumatoid factor, immunoglobulin complexes, antinuclear antibody test (ANA), and complement levels (which would be diminished) - In suspected rheumatologic causes
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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. [15] 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:
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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 [16]
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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
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Cell count - Elevated leukocytes (ie, >10,000) with neutrophil predominance suggests bacterial or rheumatic cause, although unreliable
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Gram stain - Specific (but insensitive) indicator of bacterial infection
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Cultures - Signal and identify infectious etiology
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Fluid hematocrit for bloody aspirates - Hemorrhagic fluid hematocrits are usually significantly less than simultaneous peripheral blood hematocrits
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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:
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Viral cultures
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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 or gamma interferon (IFN) 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. [16] This can be more diagnostic when combined with pericardioscopy. [17]
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.) [18]
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.) [19]
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 a clincial (not echocardiographic) diagnosis. These findings include the following:
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Collapse of the right atrium, especially if it lasts for a third of the cardiac cycle
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Diastolic collapse of the right ventricle
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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:
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Presence of a coagulum in the pericardial space indicating a bloody pericardial effusion (aortic dissection, postoperative, or after other catheter-based procedures)
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Presence of a pacemaker lead either in the vicinity or inside an area of localized effusion, indicating lead perforation as a cause
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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 [20] :
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Type A - No effusion
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Type B - Separation of epicardium and pericardium
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Type C1 - Systolic and diastolic separation of pericardium
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Type C2 - Systolic and diastolic separation of pericardium, attenuated pericardial motion
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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. [21]
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. [18, 22, 23]
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. [24]
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. [25]
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 most 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:
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Stage I - Diffuse ST-segment elevation and PR-segment depression
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Stage II - Normalization of the ST and PR segments
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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
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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. [26]
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. [27]
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.
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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.
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Echocardiogram (parasternal, long axis) of a patient with a moderate pericardial effusion.
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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).
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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.
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Subcostal view of an echocardiogram that shows a moderate to large amount of pericardial effusion.
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This echocardiogram shows a large amount of pericardial effusion (identified by the white arrows).
