Pericardial Effusion Workup

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.

The following lab studies may be performed in patients with suspected pericardial effusion.

• Electrolytes - Metabolic abnormalities (eg, renal failure)
• CBC count with differential - Leukocytosis for evidence of infection, as well as cytopenias, as signs of underlying chronic disease (eg, cancer, HIV)
• Cardiac enzymes: 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 have normal coronary angiograms. An elevated troponin level in acute pericarditis typically returns to normal within 1-2 weeks and is not associated with a worse prognosis.
• Thyroid-stimulating hormone - Thyroid-stimulating hormone screen for hypothyroidism
• Rickettsial antibodies - If high index of suspicion of tick-borne disease
• Rheumatoid factor, immunoglobulin complexes, antinuclear antibody test (ANA), and complement levels (which would be diminished) - In suspected rheumatologic causes
• PPD and controls
• Pericardial fluid analysis - Routine tests (these should 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
    • Total protein fluid-to-serum ratio >0.5
    • LDH fluid-to-serum ratio >0.6
    • LDH fluid level exceeds two thirds of upper-limit of normal serum level
  • 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 - Signals and identifies infectious etiology
  • Fluid hematocrit for bloody aspirates - Hemorrhagic fluid hematocrits usually significantly less than simultaneous peripheral blood hematocrits
• Pericardial fluid - Special tests (these should be considered individually based on the pretest probability of the coexisting condition under concern)

  • 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 histological 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.
• Tumor markers: Elevated carcinoembryonic antigen (CEA) levels in pericardial fluid have a high specificity for malignant effusions.

Chest radiography

• Findings include enlarged cardiac silhouette (so-called water-bottle heart) and pericardial fat stripe.Image is from a patient with malignant pericardial effusion. Note the "water-bottle" appearance of the cardiac silhouette in the anteroposterior (AP) chest film.
• A third of patients have a coexisting pleural effusion.
• Radiography is unreliable in establishing or refuting diagnosis of pericardial effusion.

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 to altered hemodynamics can be evaluated with echocardiography.^[9]

• 2-D 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. 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, and greater than 20 mm indicates a large effusion. Fluid adjacent to the right atrium is an early sign of pericardial effusion.^[10]
  • Severe cases may be accompanied by diastolic collapse of the right atrium and right ventricle (and in hypovolemic patients, the left atrium and left ventricle), signaling the onset of pericardial tamponade (see Cardiac Tamponade). 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).
• M-mode echocardiography

  • M-mode is adjunctive to 2D imaging for the detection of pericardial effusion. Effusions can be classified using M-mode according to a system proposed by Horowitz, et al.^[11]
    • 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 view, discordant changes in right and left ventricular cavity size can suggest pronounced interventricular dependence.
• Doppler echocardiography

  • Transmitral and transtricuspid inflow velocities should be interrogated to assess for respiratory variation. Decreases in flow during inspiration (transmitral) or expiration (transtricuspid) should raise the suspicion of clinically significant interventricular dependence and tamponade physiology.
  • Pulmonic vein inflow may show a decrease in early diastolic flow with hemodynamically significant effusions. Hepatic vein diastolic flow reversal may also be seen.

False-positive echocardiograms can occur in pleural effusions, pericardial thickening, increased epicardial fat tissue, atelectasis, and mediastinal lesions.

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 distinguish it from an effusion, which is generally echolucent and motionless.^[9]

In addition to its mimicry, pericardial fat accumulation is a source of bioactive molecules, is significantly associated with obesity-related insulin resistance, and may be a coronary risk factor.^{[12, 13]}

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.

Transesophageal echocardiography (TEE)

TEE maintains all of the advantages of transthoracic echocardiography and is useful in characterizing loculated effusions. However, this may be difficult to perform in patients with symptomatic effusions due to hemodynamic instability, making the required sedation more difficult.

Intracardiac echocardiography (ICE)

ICE is generally reserved for the assessment of pericardial effusion in the setting of percutaneous interventional or electrophysiology procedure. Phased array ICE systems can perform both 2-D and Doppler interrogations.

Computed tomography

• CT can potentially determine composition of fluid and may detect as little as 50 mL of fluid.
• CT can detect pericardial calcifications, which can be indicative of constrictive pericarditis.
• CT results in fewer false-positive results than echocardiography.
• CT can be problematic in patients who are unstable given the time required to transport to and from the scanner and perform the test.

Magnetic resonance imaging

• MRI can detect as little as 30 mL of pericardial fluid.
• May be able to distinguish hemorrhagic and no hemorrhagic fluids, as hemorrhagic fluids have a high signal intensity on T-1 weighted images, whereas no hemorrhagic 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 than CT scan acutely, given the length of time the patient must remain in the scanner.

Both MRI and CT scan may be superior to echocardiography in detecting loculated pericardial effusions, especially when located anteriorly. Also, these modalities allow for greater visualization of the thoracic cavity and adjacent structures, and therefore may identify other abnormalities relating to the cause of the effusion.

Electrocardiography

• Early in the course of acute pericarditis, the ECG typically displays diffuse ST elevation in association with PR depression. The ST elevation is usually present in all leads except for aVR, but postmyocardial infarction pericarditis, the changes may be more localized. Classically, the ECG changes of acute pericarditis evolve through 4 progressive stages:

  • 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
  • Stage IV - Normalization of the T wavesThis 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.
• Patients with uremic pericarditis frequently do not have the typical ECG abnormalities.

• 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 include impending hemodynamic compromise (ie, pericardial tamponade), suspected infectious etiology, and uncertain etiology.
  • Use of a needle that is at least 5 cm long, 16-gauge in diameter, and 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 when 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 within 90 days may be as high as 90% in patients with cancer.
• Balloon pericardotomy

  • A catheter is placed in the pericardial space under fluoroscopy, which, after inflation of the balloon, creates a channel for passage of fluid into the pleural space, where reabsorption occurs more readily.
  • This may be useful for recurrent effusions.
• 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 as high as 91% at 30 days.
• Pericardioscopy

  • This procedure is not universally available.
  • It may increase diagnostic sensitivity in cases of unexplained pericardial effusions. It allows for visualization of pericardium and for pericardial biopsies.
• CT-guided pericardiostomy

  • Patients with effusions after cardiothoracic surgery often have limited echocardiographic windows, loculated effusions, and may be on continued ventilatory support, all of which increase the difficulty of echo-guided pericardiocentesis.
  • A report by Palmer et al suggests that, in postsurgical cases, CT-guided pericardial drainage is safe and effective. The authors reported on 36 patients—33 who underwent major cardiothoracic surgery and 3 who were treated with minimally invasive procedures—whose symptomatic pericardial effusions were drained using CT-guided percutaneous placement of an indwelling pericardial catheter. 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.^[14]