What is pericardial effusion?

Pericardial Effusion

Definition and Pathophysiology

Pericardial effusion is an abnormal accumulation of fluid in the pericardial space exceeding the normal 10-50 mL of plasma ultrafiltrate that normally lubricates the pericardial layers. 1

The fluid accumulates through two primary mechanisms:

• Increased production (exudate) from inflammatory processes causing pathological fluid secretion 1
• Decreased reabsorption (transudate) from elevated systemic venous pressure in conditions like heart failure or pulmonary hypertension 1

Classification Systems

By Size (Echocardiographic Assessment)

• Mild: <10 mm separation 1
• Moderate: 10-20 mm separation 1
• Large/Severe: >20 mm separation 1

By Duration

• Acute or subacute: Present for days to weeks 1
• Chronic: Persisting >3 months 1

By Distribution

• Circumferential: Fluid surrounds the entire heart 1
• Loculated: Fluid confined to specific pockets 1

By Composition

• Exudate: High protein/fibrin content from inflammation, infection, or malignancy 2
• Transudate: Low protein content from heart failure 2
• Hemorrhagic: Blood-containing fluid from trauma, malignancy, or post-procedural complications 3
• Purulent: Pus from bacterial infection 1

Etiology

Geographic Variation in Causes

In developed countries, up to 50% of cases remain idiopathic despite comprehensive evaluation, while tuberculosis dominates in developing countries, accounting for >60% of cases in endemic regions. 1, 4, 3

Major Etiologic Categories

Infectious (15-30% in developed countries):

• Viral: Enteroviruses, echoviruses, adenoviruses, CMV, EBV, HSV, influenza, parvovirus B19, hepatitis C, HIV 4
• Tuberculosis: Leading cause worldwide and in HIV-endemic areas 4, 3
• Bacterial and fungal: Particularly in immunocompromised patients 4

Neoplastic (10-25% in developed countries):

• Secondary metastatic tumors (40 times more common than primary): Lung cancer, breast cancer, lymphoma, malignant melanoma, leukemias 4, 3
• Primary pericardial tumors: Mesothelioma (rare) 4
• Critical caveat: In almost two-thirds of patients with documented malignancy, pericardial effusion is caused by non-malignant diseases such as radiation pericarditis or opportunistic infections 4

Autoimmune/Inflammatory (5-15%):

• Systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, systemic vasculitides 1, 4
• Sarcoidosis 4
• Post-cardiac injury syndromes (post-MI, post-pericardiotomy, post-traumatic) 4

Metabolic/Endocrine:

• Hypothyroidism: Occurs in 5-30% of hypothyroid patients; effusions may be quite large but tamponade is rare, characterized by relative bradycardia and low QRS voltage 1, 4, 5
• Uremia: Common in end-stage renal disease patients 4, 5

Cardiovascular:

• Pulmonary arterial hypertension: Effusion occurs in 25-30% of cases, typically small but portends poor prognosis even when mild 1, 4
• Heart failure: Causes transudative effusion from increased venous pressure 4, 3
• Aortic dissection: Hemopericardium occurs in 17-45% of ascending aortic dissections 4

Iatrogenic/Traumatic (15-20%):

• Cardiac surgery, PCI, pacemaker insertion, radiofrequency ablation 4
• Penetrating or non-penetrating thoracic trauma 4, 3
• Radiation therapy (6-30% of patients) 4
• Chemotherapy agents: Anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib 4

Drug-Related:

• Lupus-like syndrome: Procainamide, hydralazine, methyldopa, isoniazid, phenytoin 4
• Other medications: Amiodarone, methysergide, mesalazine, clozapine, minoxidil 4

Clinical Presentation

Symptom Variability Based on Accumulation Rate

The clinical presentation varies dramatically according to the speed of fluid accumulation. 1

Rapid accumulation (trauma, iatrogenic perforation):

• Even small amounts (50-100 mL) cause dramatic symptoms within minutes 1
• Progresses rapidly to overt cardiac tamponade 1

Slow accumulation (chronic effusions):

• Large volumes can collect over days to weeks before symptoms develop 1
• Many patients remain asymptomatic and effusion is an incidental finding on imaging 1

Classic Symptoms

• Dyspnea on exertion progressing to orthopnea 1
• Chest pain and/or fullness 1

Compression Symptoms

• Nausea (diaphragm compression) 1
• Dysphagia (esophageal compression) 1
• Hoarseness (recurrent laryngeal nerve compression) 1
• Hiccups (phrenic nerve compression) 1

Non-Specific Symptoms

• Cough, weakness, fatigue, anorexia, palpitations (reflecting compressive effects or reduced blood pressure with secondary sinus tachycardia) 1
• Fever suggests infectious or immune-mediated pericarditis 1

Physical Examination Findings

• May be completely normal in patients without hemodynamic compromise 1
• When tamponade develops: Neck vein distension with elevated JVP, pulsus paradoxus (>10 mmHg inspiratory decrease in systolic BP), diminished heart sounds 1
• Pericardial friction rubs are rarely heard; typically detected only with concomitant pericarditis 1

Diagnostic Approach

Initial Diagnostic Workup

Transthoracic echocardiography is the primary diagnostic tool and is recommended in all patients with suspected pericardial effusion. 1 It provides:

• Semiquantitative size assessment 1
• Hemodynamic impact evaluation 1
• Detection of chamber collapse 6

Chest X-ray is recommended to assess for pleuropulmonary involvement and shows enlarged cardiac silhouette with slow-accumulating effusions 1

Assessment of inflammatory markers (CRP) is recommended in all patients with pericardial effusion 1

CT or CMR should be considered for suspected loculated effusions, pericardial thickening, masses, or associated chest abnormalities 1

Clinical Triage Based on Presentation

Key diagnostic algorithm from ESC guidelines: 4

If cardiac tamponade WITHOUT inflammatory signs:

• Likelihood ratio 2.9 for neoplastic etiology 4, 3
• Requires emergency drainage 1

If severe effusion WITHOUT tamponade and WITHOUT inflammatory signs:

• Likelihood ratio 20 for chronic idiopathic etiology 4, 3

If inflammatory signs present (chest pain, fever, pericardial friction rub, elevated CRP):

• Manage as pericarditis 1, 4

Specific Testing Based on Clinical Suspicion

Immediate TSH measurement is warranted as hypothyroidism is a reversible cause 5

Renal function assessment (BUN, creatinine, dialysis status) for uremic causes 5

Malignancy evaluation if constitutional symptoms, history of cancer, or tamponade without inflammation 5, 3

Autoimmune screening (ANA, RF, complement levels) if clinically indicated 5

Hemodynamic Consequences

Cardiac Tamponade

Cardiac tamponade is a life-threatening compression of the heart due to pericardial accumulation of fluid, pus, blood, clots, or gas. 1

The magnitude of hemodynamic abnormalities depends on:

• Rate of fluid accumulation 1
• Amount of pericardial contents 1
• Distensibility of the pericardium 1
• Filling pressures and compliance of cardiac chambers 1

Tamponade is a "last-drop" phenomenon: The pericardial pressure-volume curve shows an initial slow ascent followed by an almost vertical rise, meaning the final fluid increment produces critical cardiac compression. 1

Special Consideration in Pulmonary Arterial Hypertension

Diagnosing tamponade in severe PAH is challenging because high right-sided pressures mask typical findings. 1

• Right-sided chamber collapse is uncommon due to elevated intracardiac pressures 1
• Left atrial early diastolic collapse is more commonly seen (since left atrial pressure is typically lower in PAH) 1
• Exaggerated ventricular interdependence may be present 1

Prognosis and Natural History

Risk Stratification by Size and Duration

Mild idiopathic effusions (<10 mm):

• Usually asymptomatic 1
• Generally good prognosis 1
• Do not require specific monitoring 1

Moderate to large effusions (>10 mm):

• May worsen over time 1
• Appropriate echocardiographic follow-up: every 6 months for moderate effusions 1

Severe effusions:

• May evolve to cardiac tamponade in up to one-third of cases 1, 7, 8
• Echocardiographic follow-up: every 3-6 months 1

Large chronic effusions (>3 months):

• 30-35% risk of progression to cardiac tamponade 1, 7
• Well tolerated for long periods in most patients, but severe tamponade can develop unexpectedly at any time 8

Prognostic Implications in Specific Conditions

In pulmonary arterial hypertension, even small pericardial effusion portends poor prognosis and is associated with:

• Connective tissue disease 1
• Shorter 6-minute walk distance 1
• Elevated B-type natriuretic peptide 1
• Marker of high venous pressure or comorbidity 1

Documented idiopathic pericarditis has very low risk of constrictive pericarditis despite several recurrences; risk is related to etiology, not number of recurrences. 1

Common Pitfalls and Caveats

Serosanguinous or hemorrhagic fluid appearance alone cannot determine etiology, as it occurs in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral effusions. 4, 3

In patients with documented malignancy, do not automatically assume malignant effusion: Almost two-thirds are caused by non-malignant diseases such as radiation pericarditis, other therapies, or opportunistic infections. 4

Pericardial effusion is often associated with known or unknown medical conditions in up to 60% of cases, requiring systematic evaluation for underlying systemic disease. 1, 4

Subacute large effusions (4-6 weeks) not responsive to conventional therapy with echocardiographic signs of right chamber collapse may have increased risk of progression, and some authors recommend preventive drainage. 1