What are the causes of pericardial effusion?

Causes of Pericardial Effusion

Pericardial effusion arises from infectious, neoplastic, autoimmune, metabolic, iatrogenic, and idiopathic causes, with the specific etiology heavily dependent on geographic location—tuberculosis dominates in developing countries (>60% of cases), while viral infections, malignancy, and idiopathic causes are most common in developed nations. 1, 2

Geographic and Epidemiologic Framework

The distribution of pericardial effusion causes varies dramatically by region:

• In developing countries: Tuberculosis accounts for over 60% of cases, particularly in HIV-endemic regions of sub-Saharan Africa 1, 2, 3
• In developed countries: The etiology is more heterogeneous, with up to 50% remaining idiopathic despite comprehensive evaluation 2, 4, 3
• Viral infections are the most common infectious cause in developed countries 1, 2, 4

Major Etiologic Categories

Infectious Causes

Viral infections represent the leading infectious etiology in developed nations and include:

• Enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza virus, parvovirus B19, hepatitis C virus, and HIV 2, 4

Bacterial infections:

• Tuberculosis is the most frequent cause worldwide and in developing countries, often associated with HIV co-infection 1, 2
• Untreated tuberculous pericarditis carries an 85% mortality rate, with pericardial constriction occurring in 30-50% of cases 1

Fungal infections occur particularly in immunocompromised patients 4

Neoplastic Causes

Malignancy accounts for 10-25% of pericardial effusions in developed countries and is the most common cause of cardiac tamponade among medical patients (likelihood ratio 2.9) 2, 4, 3:

• Secondary metastatic tumors are 40 times more common than primary pericardial tumors 2, 4, 3
• Most common malignancies: Lung cancer, breast cancer, lymphoma, malignant melanoma, and leukemias 2, 4
• Primary pericardial tumors are rare, with mesothelioma being the most common 4

Critical caveat: In almost two-thirds of patients with documented malignancy, pericardial effusion is actually caused by non-malignant diseases such as radiation pericarditis, other therapies, or opportunistic infections 4

Autoimmune and Inflammatory Disorders

Systemic autoimmune diseases account for 5-15% of cases in developed countries 2, 4, 3:

• Systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, systemic vasculitides (eosinophilic granulomatosis with polyangiitis, Horton disease, Takayasu disease, Behçet syndrome), and sarcoidosis 1, 4

Post-cardiac injury syndromes have an autoimmune pathogenesis 2:

• Post-myocardial infarction syndrome (Dressler syndrome) 1
• Post-pericardiotomy syndrome (more common after valve surgery than CABG) 1
• Post-traumatic pericarditis, including iatrogenic trauma from coronary intervention, pacemaker lead insertion, or radiofrequency ablation 1

Metabolic and Endocrine Disorders

Renal failure is a major metabolic cause with two distinct forms 1:

• Uremic pericarditis: Occurs in 6-10% of patients with advanced renal failure (BUN >60 mg/dL) before or shortly after dialysis initiation 1
• Dialysis-associated pericarditis: Affects up to 13% of patients on maintenance hemodialysis, due to inadequate dialysis and/or fluid overload 1

Hypothyroidism:

• Occurs in 5-30% of hypothyroid patients, characterized by large effusions but tamponade is rare 2, 4, 3
• ECG shows relative bradycardia and low QRS voltage 4

Other metabolic causes include myxedema, anorexia nervosa 1

Iatrogenic and Traumatic Causes

Direct injury (rare):

• Penetrating thoracic injury, esophageal perforation 1, 4, 3
• Immediate thoracotomy is indicated for cardiac tamponade due to penetrating trauma 4

Indirect injury:

• Non-penetrating thoracic injury, radiation injury (occurs in 6-30% of patients receiving radiation therapy) 1, 4

Delayed onset post-procedural:

• Coronary percutaneous intervention, pacemaker lead insertion, radiofrequency ablation 1

Drug-Related Causes

Lupus-like syndrome: Procainamide, hydralazine, methyldopa, isoniazid, phenytoin 1, 4

Antineoplastic drugs (often associated with cardiomyopathy): Doxorubicin, daunorubicin, anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib, interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, osimertinib 1, 4

Other medications: Amiodarone, methysergide, mesalazine, clozapine, minoxidil, thiazides, streptomycin, cyclosporine, bromocriptine, vaccines, GM-CSF, anti-TNF agents 1, 4

Cardiovascular Causes

• Heart failure: Causes transudative effusion due to increased systemic venous pressure and decreased reabsorption 2, 4, 3
• Pulmonary arterial hypertension: Effusion occurs in 25-30% of cases, typically small and rarely causing hemodynamic compromise 2, 4, 3
• Aortic dissection: Hemopericardium occurs in 17-45% of patients with ascending aortic dissection 4
• Post-myocardial infarction: Pericardial effusion >10 mm is most frequently associated with hemopericardium, and two-thirds may develop tamponade or free wall rupture 4

Rare Specific Types

Chylopericardium: Pericardial effusion composed of chyle due to injury or blockage of the thoracic duct from trauma, surgery, congenital lymphangiomatosis, radiotherapy, subclavian vein thrombosis, infection, mediastinal neoplasms, or acute pancreatitis 4

Cholesterol pericarditis: Occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma 4

Clinical Diagnostic Pearls

When cardiac tamponade presents without inflammatory signs (no chest pain, fever, pericardial friction rub, or elevated CRP), suspect neoplastic etiology (likelihood ratio 2.9) 2, 4

When severe effusion exists without cardiac tamponade and without inflammatory signs, chronic idiopathic etiology is most likely (likelihood ratio 20) 2, 4

If inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP), manage as pericarditis 4, 3

Important Caveats

• Fluid appearance is not diagnostic: Serosanguinous or hemorrhagic fluid can occur in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral effusions 4, 3
• Large chronic effusions (>3 months) carry up to one-third risk of progression to cardiac tamponade 3, 5
• Pericardial effusion is often associated with known or unknown medical conditions in up to 60% of cases 4
• In uremic patients, autonomic impairment may cause heart rate to remain slow (60-80 beats/min) during tamponade despite fever and hypotension 1
• ECG in uremic pericarditis does not show typical diffuse ST/T wave elevations due to lack of myocardial inflammation; if typical ECG changes are present, suspect intercurrent infection 1