Malignant Pericardial Effusion

Malignant pericardial effusion is fluid in the pericardial sac caused by metastasis to, or direct invasion of, the pericardium, or by tumour obstruction of lymphatic drainage. It can progress to cardiac tamponade, which is life threatening and needs urgent drainage.

Malignancy accounts for about 10 to 25% of large pericardial effusions in developed settings. Cancers responsible are lung (about 40%), breast (about 20%), haematological malignancy (lymphoma and leukaemia), oesophageal, melanoma, ovarian, and gastric tumours. Primary pericardial mesothelioma is rare.

Effusion may be the first presentation of cancer in a minority of patients. Not every effusion in a cancer patient is malignant: radiation pericarditis, drug toxicity, infection (including tuberculosis), hypothyroidism and idiopathic effusion all occur and must be excluded.

Median survival with a malignant effusion is short (about 2 to 8 months overall), longer with chemosensitive tumours (lymphoma, breast) and shorter with lung cancer.

Pathophysiology.

Tumour deposits on the pericardium produce exudative fluid, and obstruction of pericardial lymphatics and mediastinal lymph nodes reduces fluid clearance. Fluid is often bloody.

Rapid accumulation of fluid beyond the stretch of the pericardium raises intrapericardial pressure over the diastolic filling pressures, first of the right atrium and ventricle, causing tamponade. Malignant effusions often accumulate slowly, so large volumes can be tolerated before tamponade appears, but tumour thickening and loculation make drainage difficult.

Recurrence is high after simple drainage because the underlying pericardial disease continues.

Dyspnoea, orthopnoea, cough, chest discomfort, fatigue, weight loss and peripheral oedema, often in a patient with known cancer. Tamponade shows Beck triad (hypotension, raised jugular venous pressure, muffled heart sounds), tachycardia, pulsus paradoxus (inspiratory fall in systolic pressure of more than 10 mmHg), narrow pulse pressure, oliguria and cool peripheries. Signs can be subtle in slowly accumulating effusions. Superior vena cava obstruction, pleural effusion and a pericardial friction rub may be present.

• Echocardiography: size of the effusion (large when over 20 mm in diastole), loculation, thickened or nodular pericardium, right atrial and right ventricular diastolic collapse, plethoric inferior vena cava, and respiratory variation of mitral and tricuspid inflow (over 25% and over 40% respectively) indicating tamponade.
• ECG: sinus tachycardia, low voltage, and electrical alternans (specific for large effusion).
• Chest radiograph: globular heart, pleural effusion, mediastinal mass. CT chest, abdomen and pelvis for the primary tumour and extent of disease. MRI or PET-CT where needed.
• Pericardiocentesis for symptomatic effusion: fluid is usually an exudate (protein over 30 g/L, fluid-to-serum protein ratio over 0.5, LDH over 200 U/L, or fluid-to-serum LDH ratio over 0.6), frequently bloody. Cytology confirms malignancy in about 70 to 90%. Send cytology (with cell block and immunostaining), culture, mycobacterial testing (Xpert and culture), adenosine deaminase (over 40 U/L suggests tuberculosis), cell count, and tumour markers (carcinoembryonic antigen over 5 microgram/L supports adenocarcinoma).
• Pericardial biopsy (surgical window or thoracoscopic) when cytology is negative and malignancy remains likely, or a diagnosis is needed.
• Blood tests: full blood count, creatinine, liver tests, TSH, HIV test (in endemic regions), and troponin.

Differential diagnosis.

• Radiation pericarditis and drug induced effusion (anthracyclines, immune checkpoint inhibitors, cyclophosphamide, dasatinib).
• Tuberculous or bacterial pericarditis.
• Hypothyroid, uraemic, autoimmune and idiopathic effusion.
• Heart failure and nephrotic syndrome, and superior vena cava syndrome.

Tamponade (emergency).

• Urgent pericardiocentesis under echocardiographic control by an experienced operator, using the subcostal or apical approach. Leave a pigtail catheter (6 to 8 Fr) in place for 3 to 7 days, and remove it when drainage falls under 25 mL in 24 hours (or under 50 mL in 24 hours in cancer patients in some centres), with repeat echocardiography before removal.
• Meanwhile: oxygen, intravenous crystalloid 250 to 500 mL over 10 to 15 minutes to support filling (temporary), and noradrenaline 0.05 to 0.5 microgram/kg/min if hypotensive. Avoid diuretics, vasodilators and beta blockers. Avoid intubation and positive pressure ventilation, which can precipitate arrest.
• Drain slowly in large effusions (drain no more than 1 litre at the first sitting, then the remainder over hours) to avoid pericardial decompression syndrome (acute ventricular dysfunction, pulmonary oedema). Monitor for re-accumulation, haemothorax and cardiac injury.
• When cancer anticoagulation or antiplatelet therapy is in use, hold it during and after drainage.

Asymptomatic or minimally symptomatic effusion without tamponade. Treat the underlying cancer (systemic chemotherapy, hormonal or targeted therapy, immunotherapy) and observe with echocardiography every 1 to 4 weeks initially. Diagnostic pericardiocentesis is performed when the cause is unknown or the effusion is large (over 20 mm in diastole).

Preventing recurrence (recurrence is common, 40 to 70% after drainage alone).

• Extended catheter drainage for 3 to 7 days or longer, which lowers recurrence.
• Intrapericardial instillation of a sclerosing or cytotoxic agent through the drain: cisplatin (lung and other adenocarcinoma) or thiotepa (breast cancer), under oncology and cardiology direction with agent, dose and dwell time set by the centre's regimen. Intrapericardial agents can cause pain, fever, arrhythmia and constrictive pericarditis, so use is limited to selected patients.
• Percutaneous balloon pericardiotomy, where available, creates a pericardial window.
• Surgical pericardial window (subxiphoid or video assisted thoracoscopic) for recurrent or loculated effusion in patients with a reasonable life expectancy; it also provides tissue.
• Radiotherapy for radiosensitive tumours (lymphoma, leukaemia) with effusion, and systemic therapy for chemosensitive tumours.
• Pericardiectomy is seldom used and only for constriction with a reasonable prognosis.

Supportive and adjunctive treatment. Colchicine and non-steroidal anti-inflammatory drugs are not effective in malignant effusion. Corticosteroids are used only when the tumour is steroid responsive (lymphoma). Palliative care involvement early, with a clear goals-of-care discussion, because prognosis is often limited.

Monitoring. Echocardiography at 24 to 48 hours after drainage, before drain removal, at 1 week, and then every 1 to 3 months for 6 months; clinical review for dyspnoea, hypotension and weight gain; drain output twice daily.

Referral and escalation. Refer immediately to cardiology and oncology for any effusion in a cancer patient with haemodynamic compromise, or any large effusion. Same day drainage for tamponade physiology. Refer for surgical or percutaneous pericardial window when effusion recurs after drainage.

Special groups.

• Pregnancy: rare; manage with a multidisciplinary team; avoid cisplatin and thiotepa where possible.
• Older adults and frailty: prefer minimally invasive options; discuss goals of care.
• Kidney impairment: platinum agents need dose adjustment and hydration; avoid nephrotoxic contrast.
• Region specific: in tuberculosis endemic and HIV-endemic regions, tuberculous and HIV-related pericardial effusion are more common than malignant effusion, so tuberculosis testing and HIV testing are part of every workup.