Causes of Pericardial Effusion
Geographic and Epidemiologic Context
Tuberculosis is the dominant cause of pericardial effusion worldwide and in developing countries, accounting for over 60% of cases in endemic regions, while in developed countries up to 50% of cases remain idiopathic despite comprehensive evaluation. 1, 2
Major Etiologic Categories
Infectious Causes
Viral infections are the most common infectious etiology in developed countries, including: 2
- Enteroviruses, echoviruses, adenoviruses
- Cytomegalovirus, Epstein-Barr virus, herpes simplex virus
- Influenza virus, parvovirus B19
- Hepatitis C virus and HIV
Tuberculosis remains the leading cause globally, particularly in HIV-coinfected patients and endemic areas. 2
Bacterial and fungal infections can cause pericardial effusion, especially in immunocompromised patients. 2
Neoplastic Causes (10-25% of cases in developed countries)
Secondary metastatic tumors are far more common than primary pericardial tumors (40 times more frequent): 2
- Lung cancer (most common)
- Breast cancer
- Lymphoma and leukemia
- Malignant melanoma
Primary pericardial tumors are rare, with mesothelioma being the most common primary malignant tumor. 2
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 cancer therapies, or opportunistic infections—not the malignancy itself. 2
Autoimmune and Inflammatory Disorders (5-15% of cases)
Systemic autoimmune diseases that cause pericardial effusion include: 1, 2
- Systemic lupus erythematosus
- Sjögren syndrome
- Rheumatoid arthritis
- Scleroderma
- Systemic vasculitides
- Sarcoidosis
Post-cardiac injury syndromes: 2
- Post-myocardial infarction pericarditis (effusion >10 mm frequently associated with hemopericardium; two-thirds may develop tamponade or free wall rupture)
- Post-pericardiotomy syndrome
- Post-traumatic pericarditis
Metabolic and Endocrine Disorders
Hypothyroidism is the main metabolic cause, occurring in 5-30% of patients with hypothyroidism; effusions may be quite large but tamponade occurs rarely. 1, 2 Diagnosis is confirmed by elevated TSH, with clinical features including relative bradycardia and low QRS voltage on ECG. 1
Uremia in end-stage renal disease causes pericardial effusion in up to 20% of patients, presenting as either uremic pericarditis or dialysis-associated pericarditis. 3
Cardiovascular Causes
Pulmonary arterial hypertension is associated with pericardial effusion in 25-30% of cases, typically small in size but rarely causing hemodynamic compromise. 1, 2 The mechanism relates to right ventricular failure, increased right-sided filling pressures, and lymphatic obstruction. 1
Heart failure causes transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption. 1, 2
Aortic dissection with hemopericardium occurs in 17-45% of patients with ascending aortic dissection. 2
Iatrogenic and Traumatic Causes (15-20% of cases)
Direct injury: 2
- Penetrating thoracic injury (requires immediate thoracotomy if tamponade develops)
- Esophageal perforation
Post-procedural complications: 2
- Cardiac surgery
- Percutaneous coronary intervention
- Pacemaker lead insertion
- Radiofrequency ablation
Radiation therapy causes pericardial effusion and/or constriction in 6-30% of patients, often developing years after treatment. 2
Chemotherapy-associated causes include: 2
- Anthracyclines (doxorubicin, daunorubicin)
- Cyclophosphamide, cytarabine
- Tyrosine kinase inhibitors (imatinib, dasatinib, osimertinib)
- Interferon-α, arsenic trioxide
- 5-fluorouracil, docetaxel
Drug-Induced Causes
Lupus-like syndrome: procainamide, hydralazine, methyldopa, isoniazid, phenytoin 2
Other medications: amiodarone, methysergide, mesalazine, clozapine, minoxidil, thiazides, cyclosporine, anti-TNF agents, GM-CSF 2
Rare Specific Types
Chylopericardium is composed of chyle from thoracic duct injury, caused by: 1, 2
- Trauma or surgery (especially congenital heart disease)
- Congenital lymphangiomatosis
- Radiotherapy
- Subclavian vein thrombosis
- Mediastinal neoplasms
- Acute pancreatitis
Cholesterol pericarditis occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma (distinct from chylopericardium). 1, 2
Important Clinical Pitfalls
Anticoagulation is not a risk factor for hemorrhagic pericardial effusion or tamponade in acute pericarditis based on multivariable analysis of nearly 500 consecutive cases; however, full anticoagulation may be a risk factor in iatrogenic pericardial effusion. 1
Fluid appearance cannot determine etiology: serosanguinous or hemorrhagic fluid can occur in malignant, post-pericardiotomy, rheumatologic, traumatic, and iatrogenic effusions, but also in idiopathic and viral forms. 2