Pericardial Effusion Causes and Associations

Introduction to Pericardial Effusion

• The European Society of Cardiology notes that the most common causes of pericardial effusion include infectious diseases, neoplastic conditions, autoimmune disorders, metabolic/endocrine disorders, iatrogenic/traumatic injuries, and idiopathic causes 1

Infectious Causes

• Viral infections are the most common infectious etiology in developed countries, including enteroviruses, echoviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, influenza virus, parvovirus B19, hepatitis C virus, and HIV 2
• Tuberculosis is the leading cause of pericardial effusion in developing countries and worldwide, especially in areas where TB is endemic and often associated with HIV infection 1
• Fungal infections may also lead to pericardial effusion, particularly in immunocompromised patients 2

Autoimmune and Inflammatory Causes

• Systemic autoimmune diseases including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitides can cause pericardial effusion 1
• Sarcoidosis can involve the pericardium causing effusion 1
• Post-cardiac injury syndromes including post-myocardial infarction pericarditis, post-pericardiotomy syndrome, and post-traumatic pericarditis can lead to pericardial effusion 3
• Autoreactive pericarditis (immune-mediated inflammation) is another cause of pericardial effusion 2

Neoplastic Causes

• Primary tumors of the pericardium (rare, primarily pericardial mesothelioma) can cause pericardial effusion 1
• Secondary metastatic tumors (common, especially lung and breast cancer, lymphoma) are a common cause of pericardial effusion 1, 4

Metabolic and Endocrine Disorders

• Hypothyroidism is a main cause of pericardial effusion in this category, occurring in 5-30% of patients with hypothyroidism; effusions may be large but tamponade is rare 5, 3
• Uremia in patients with renal failure can cause pericardial effusion 3

Cardiovascular and Pulmonary Causes

• Pericardial effusion is common (25-30%) in pulmonary arterial hypertension, typically small in size but rarely causing hemodynamic compromise 5, 3
• Heart failure can cause transudative pericardial effusion 6

Iatrogenic and Traumatic Causes

• Direct injury: penetrating thoracic injury, esophageal perforation can cause pericardial effusion 1
• Indirect injury: non-penetrating thoracic injury, radiation injury can lead to pericardial effusion 1
• Post-procedural: cardiac surgery, percutaneous coronary intervention, pacemaker lead insertion, radiofrequency ablation can cause pericardial effusion 1
• Chemotherapy-associated: anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib, interferon-α, arsenic trioxide, docetaxel, 5-fluorouracil, osimertinib can cause pericardial effusion 4
• Radiation therapy can cause pericardial effusion and/or constriction in 6-30% of patients 4

Rare Specific Types of Pericardial Effusion

• Chylopericardium: pericardial effusion composed of chyle due to injury or blockage of the thoracic duct; causes include trauma, surgery, congenital lymphangiomatosis, radiotherapy, subclavian vein thrombosis, infection, mediastinal neoplasms, and acute pancreatitis 5, 7
• Cholesterol pericarditis: occurs in tuberculous pericarditis, rheumatoid pericarditis, and trauma 5
• Pericardial cysts: rare mediastinal masses (incidence 1 in 100,000) representing 6% of mediastinal masses and 33% of mediastinal cysts 5

Drug-Related Causes

• Lupus-like syndrome: procainamide, hydralazine, methyldopa, isoniazid, phenytoin can cause pericardial effusion 1
• Antineoplastic drugs (often associated with cardiomyopathy): doxorubicin, daunorubicin can cause pericardial effusion 1
• Other medications: amiodarone, methysergide, mesalazine, clozapine, minoxidil, dantrolene, practolol, phenylbutazone, thiazides, streptomycin, thiouracils, streptokinase, p-aminosalicylic acid, sulfa drugs, cyclosporine, bromocriptine, vaccines, GM-CSF, anti-TNF agents can cause pericardial effusion 1

Idiopathic Causes

• In developed countries, many cases remain idiopathic (up to 50%) despite comprehensive diagnostic evaluation 6

Pericardial Effusion Causes and Characteristics

Infectious and Neoplastic Causes

• Tuberculosis dominates as the cause of pericardial effusion in over 60% of cases in endemic regions 8
• Malignant effusions account for 10-25% of cases in developed countries, with lung cancer, breast cancer, malignant melanoma, lymphomas, and leukemias being the most common secondary malignant tumors causing pericardial effusion 8
• Primary tumors of the pericardium are 40 times less common than metastatic ones, with mesothelioma being the most common primary malignant tumor 9
• Critically, in almost two-thirds of patients with documented malignancy, pericardial effusion is caused by non-malignant diseases such as radiation pericarditis, other therapies, or opportunistic infections 10

Autoimmune, Metabolic, and Cardiovascular Causes

• Systemic autoimmune diseases including systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitides can cause pericardial effusion, accounting for 5-15% of cases 8
• Heart failure can cause transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 8
• Aortic dissection with hemopericardium occurs in 17-45% of patients with ascending aortic dissection 9

Iatrogenic and Traumatic Causes

• Immediate thoracotomy is indicated in cardiac tamponade due to penetrating trauma 11
• Post-myocardial infarction: pericardial effusion >10 mm is most frequently associated with hemopericardium, and two-thirds may develop tamponade or free wall rupture 9

Clinical Characteristics

• Serosanguinous or hemorrhagic fluid can be found in malignant, post-pericardiotomy, rheumatologic, traumatic, and iatrogenic effusions, but also in idiopathic and viral forms, so fluid appearance alone cannot determine etiology 12

Pericardial Effusion Causes and Clinical Pearls

Introduction to Pericardial Effusion

• Cardiac tamponade without inflammatory signs is associated with a higher risk of neoplastic etiology (likelihood ratio 2.9), according to the European Society of Cardiology 13
• Severe effusion without cardiac tamponade and inflammatory signs is usually associated with chronic idiopathic etiology (likelihood ratio 20), as stated by the European Heart Journal 13
• Pericardial effusion is often associated with known or unknown medical conditions in up to 60% of cases, as reported by the European Heart Journal 13
• If inflammatory signs are present (chest pain, fever, pericardial friction rub, elevated CRP), clinical management should follow that of pericarditis, as recommended by the European Heart Journal 13

Pericardial Effusion Causes

Etiology and Epidemiology

• The European Society of Cardiology notes that pericardial effusion causes vary by geographic region, with tuberculosis accounting for more than 60% of cases in developing countries, while in developed countries, idiopathic causes can account for up to 50% of cases, and cancer, infections, iatrogenic causes, and autoimmune diseases are other major etiologies 14
• The American Heart Association recommends that in developed countries, the etiology distribution is more heterogeneous, and despite comprehensive evaluation, up to 50% of cases remain idiopathic 14

Specific Etiologies

• Malignancy accounts for 10-25% of cases in developed countries, with secondary metastatic tumors being 40 times more common than primary pericardial tumors 14
• Systemic autoimmune diseases account for 5-15% of cases, including systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, scleroderma, and sarcoidosis 14
• Hypothyroidism can cause pericardial effusion in 5-30% of patients, although tamponade is rare, and is characterized by relative bradycardia and low QRS voltage on EKG 15
• Pulmonary arterial hypertension is associated with pericardial effusion in 25-30% of cases, typically small in size and rarely causing hemodynamic compromise 15

Metabolic and Endocrine Disorders

• The European Society of Cardiology states that hypothyroidism is a cause of pericardial effusion, diagnosed by high TSH levels, and characterized by relative bradycardia and low QRS voltage on EKG 15

Iatrogenic and Traumatic Causes

• The American College of Cardiology recommends that drug-related causes of pericardial effusion include lupus-like syndrome, antineoplastic drugs, and other medications 15

Cardiovascular Causes

• Heart failure can cause transudative pericardial effusion due to increased systemic venous pressure and decreased reabsorption 14
• Pulmonary arterial hypertension is associated with pericardial effusion, typically small in size, and rarely causing hemodynamic compromise, and is related to right ventricular failure and increased right-sided filling pressures 15

Etiology and Epidemiology of Pericardial Effusion

Geographic Distribution

• In developing countries, tuberculosis is responsible for >60 % of pericardial effusions, especially in HIV‑endemic sub‑Saharan Africa populations. 16
• In developed nations, the spectrum is more heterogeneous; viral infections, malignancy and idiopathic causes predominate, while tuberculosis remains the leading worldwide infectious cause. [17][16]

Infectious Causes

• Tuberculosis is the most frequent bacterial cause of pericardial effusion globally and in low‑resource settings, frequently co‑existing with HIV infection. [16][18]
• Untreated tuberculous pericarditis carries an ≈85 % mortality rate, and progresses to constrictive pericarditis in 30–50 % of cases. 18

Autoimmune and Post‑Cardiac Injury Syndromes

• Systemic autoimmune diseases (e.g., systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, systemic vasculitides, sarcoidosis) account for 5–15 % of pericardial effusions in developed countries. [17][16]
• Post‑myocardial infarction (Dressler) syndrome is an autoimmune pericardial reaction following infarction. [17][16]
• Post‑pericardiotomy syndrome occurs more often after valve surgery than after coronary artery bypass grafting. [17][16]18
• Post‑traumatic pericarditis can follow iatrogenic cardiac injury from coronary interventions, pacemaker lead placement, or radio‑frequency ablation. [17][16]

Metabolic and Renal Causes

• Uremic pericarditis develops in 6–10 % of patients with advanced renal failure (elevated BUN) before or shortly after dialysis initiation. 18
• Dialysis‑associated pericarditis affects up to 13 % of patients on maintenance hemodialysis, related to inadequate dialysis or fluid overload. 18
• In uremic patients, autonomic dysfunction may keep heart rate 60–80 bpm during tamponade despite fever and hypotension. 18
• The ECG in uremic pericarditis typically lacks diffuse ST/T elevation; presence of such changes should raise suspicion for concurrent infection. 18

Iatrogenic and Traumatic Causes

• Direct penetrating thoracic injury (e.g., stab wound, esophageal perforation) can cause acute pericardial effusion. [17][16]
• Radiation‑induced pericardial injury occurs in 6–30 % of patients receiving thoracic radiotherapy. [17][16]

Drug‑Induced Pericardial Effusion

• Lupus‑like drug reactions (procainamide, hydralazine, methyldopa, isoniazid, phenytoin) can precipitate pericardial effusion. [17][16]
• Antineoplastic agents (doxorubicin, daunorubicin, anthracyclines, cyclophosphamide, cytarabine, imatinib, dasatinib, interferon‑α, arsenic trioxide, docetaxel, 5‑fluorouracil, osimertinib) are associated with pericardial effusion, often in the context of cardiomyopathy. [17][16]
• Other medications (amiodarone, methysergide, mesalazine, clozapine, minoxidil, thiazides, streptomycin, cyclosporine, bromocriptine, vaccines, GM‑CSF, anti‑TNF agents) have been reported to cause pericardial effusion. [17][16]