What are the causes of persistent pericardial effusion?

Causes of Persistent Pericardial Effusion

Persistent pericardial effusion most commonly results from neoplastic disease, tuberculosis, uremia, hypothyroidism, autoimmune disorders, and idiopathic causes, with the specific etiology heavily dependent on geographic location and patient population. 1, 2

Geographic and Epidemiologic Considerations

The dominant causes vary dramatically by region:

• In developing countries: Tuberculosis accounts for over 60% of cases and remains the leading cause worldwide, particularly in HIV-endemic areas 2, 3
• In developed countries: Up to 50% of cases remain idiopathic despite comprehensive evaluation, while neoplastic disease accounts for 10-25% of cases 2, 4

Major Etiologic Categories

Neoplastic Causes

Malignancy is the most common cause of cardiac tamponade among medical patients and should be strongly suspected when effusion occurs without inflammatory signs (likelihood ratio 2.9). 2, 5

• Secondary metastatic tumors (40 times more common than primary): lung cancer, breast cancer, lymphoma, malignant melanoma, and leukemias 2, 6
• Primary pericardial tumors (rare): mesothelioma is the most common primary malignant tumor 2
• Critical caveat: In almost two-thirds of patients with documented malignancy, the pericardial effusion is actually caused by non-malignant etiologies such as radiation pericarditis, chemotherapy effects, or opportunistic infections 2

Infectious Causes

• Tuberculosis: Dominant cause in endemic regions and developing countries; often associated with HIV co-infection 2, 3
• Viral infections (most common infectious cause in developed countries): enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza, parvovirus B19, hepatitis C, and HIV 2
• Fungal infections: particularly in immunocompromised patients 2

Autoimmune and Inflammatory Disorders

These account for 5-15% of cases in developed countries: 2

• Systemic lupus erythematosus
• Sjögren syndrome
• Rheumatoid arthritis
• Scleroderma
• Systemic vasculitides
• Sarcoidosis
• Post-cardiac injury syndromes (post-myocardial infarction, post-pericardiotomy, post-traumatic)
• Autoreactive pericarditis 2

Metabolic and Endocrine Disorders

• Hypothyroidism: Occurs in 5-30% of hypothyroid patients; effusions may be large but tamponade is rare 2
• Uremia: Common in patients with renal failure 1, 2

Iatrogenic and Traumatic Causes

• Direct injury: penetrating thoracic trauma, esophageal perforation 2
• Indirect injury: non-penetrating thoracic trauma, radiation injury (occurs in 6-30% of patients receiving radiation therapy) 2
• Post-procedural: cardiac surgery, percutaneous coronary intervention, pacemaker insertion, radiofrequency ablation 2
• Chemotherapy-associated: anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib, interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, osimertinib 2

Cardiovascular Causes

• Heart failure: causes transudative effusion due to increased systemic venous pressure and decreased reabsorption 2
• Pulmonary arterial hypertension: effusion occurs in 25-30% of cases, typically small and rarely causing hemodynamic compromise 2
• Aortic dissection: hemopericardium occurs in 17-45% of patients with ascending aortic dissection 2

Drug-Related Causes

• Lupus-like syndrome: procainamide, hydralazine, methyldopa, isoniazid, phenytoin 2
• Antineoplastic drugs: doxorubicin, daunorubicin (often associated with cardiomyopathy) 2
• Other medications: amiodarone, methysergide, mesalazine, clozapine, minoxidil, anti-TNF agents 2

Rare Specific Types

• Chylopericardium: due to thoracic duct injury or blockage from trauma, surgery, congenital lymphangiomatosis, radiotherapy, subclavian vein thrombosis, infection, mediastinal neoplasms, acute pancreatitis 2
• Cholesterol pericarditis: occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma 2
• Pericardial cysts: rare (incidence 1 in 100,000), representing 6% of mediastinal masses 2

Clinical Pearls for Diagnosis

When inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP), manage as pericarditis. 2

Severe effusion without cardiac tamponade and without inflammatory signs is usually chronic idiopathic etiology (likelihood ratio 20). 2

In 60% of patients, the cause may be a known medical condition. 1, 2

Important Caveats

• Serosanguinous or hemorrhagic fluid appearance alone cannot determine etiology, as it occurs in malignant, post-pericardiotomy, rheumatologic, traumatic, iatrogenic, idiopathic, and viral effusions 2
• Large chronic effusions (>3 months) carry up to one-third risk of progression to cardiac tamponade 1, 4
• Massive chronic pericardial effusions are rare, representing only 2-3.5% of all large effusions 1