Viral Pericarditis

Viral pericarditis is inflammation of the pericardium caused by viral infection, or by an immune response to it. It is the commonest cause of acute pericarditis in high income settings, where most idiopathic cases are presumed to be viral.

Acute pericarditis accounts for about 5% of non-ischaemic emergency chest pain and affects mostly young adults (age 20 to 50), and men more than women. Most cases are self-limited, with a good outcome. Recurrence occurs in 15 to 30% of patients who do not receive colchicine, and constriction is rare (under 1%).

Common viruses are coxsackie B and echoviruses, adenovirus, parvovirus B19, human herpesvirus 6, Epstein-Barr virus, cytomegalovirus, influenza, hepatitis viruses, HIV and SARS-CoV-2. Pericardial involvement can accompany myocarditis (myopericarditis).

In sub-Saharan Africa and other regions with high prevalence of HIV and tuberculosis, most large effusions have a tuberculous cause, so a presumption of viral cause needs more caution.

Pathophysiology.

Direct viral injury to pericardial cells, and a subsequent immune response with cytokine release (interleukin-1, tumour necrosis factor), cause inflammation, fibrin deposition and exudate.

Inflammation of the adjacent epicardium produces ST elevation and PR depression. Fluid accumulates through increased vascular permeability, usually in small to moderate volume.

Autoimmune mechanisms may drive recurrence, which explains the response to colchicine and interleukin-1 blockade.

ECG evolves through four stages: stage I diffuse concave ST elevation with PR depression (and PR elevation in aVR); stage II return to baseline; stage III diffuse T-wave inversion; stage IV normalisation.

Sharp, pleuritic retrosternal or left sided chest pain that is worse lying flat and on inspiration, and eased by sitting forward. It may radiate to the trapezius ridge. A preceding viral illness (fever, upper respiratory or gastrointestinal symptoms, myalgia) is common. Dyspnoea, low grade fever and a pericardial friction rub (scratchy, best heard at the left sternal edge with the patient leaning forward, with up to three components) are typical.

Large effusions can cause tamponade. Troponin rise with ventricular dysfunction indicates myopericarditis.

• Diagnosis: at least 2 of (1) pericarditic chest pain, (2) pericardial friction rub, (3) new widespread ST elevation or PR depression, (4) new or worsening pericardial effusion.
• ECG: widespread concave ST elevation with PR depression, without reciprocal change (except aVR and V1), and without Q waves.
• Blood tests: C-reactive protein, ESR, white cell count, troponin (myopericarditis), creatinine, TSH, and HIV test. Autoimmune screen (antinuclear antibody) in recurrent or atypical disease.
• Chest radiograph (normal cardiac silhouette unless effusion is large), and echocardiography for effusion, tamponade, regional wall motion and left ventricular function.
• Cardiac MRI for pericardial late gadolinium enhancement and for myocardial involvement. CT for pericardial thickening or calcification.
• Tuberculosis tests (interferon gamma release assay, sputum Xpert) in endemic regions or with a large effusion, subacute onset or failure to respond.
• Pericardiocentesis only for tamponade or a large effusion (over 20 mm in diastole) with suspected purulent, tuberculous or malignant cause. Routine viral serology and viral PCR add little to management.
• Features predicting complications and favouring admission: fever over 38 degrees Celsius, subacute onset, large effusion or tamponade, failure to respond to NSAIDs after 7 days, myopericarditis, immunosuppression, oral anticoagulation and trauma.

Differential diagnosis.

• Acute myocardial infarction, myocarditis and Takotsubo syndrome.
• Early repolarisation (ST changes that are stable, with no PR depression).
• Pulmonary embolism, pneumonia with pleurisy, pneumothorax and aortic dissection.
• Oesophageal and musculoskeletal pain, and tuberculous, bacterial, uraemic, autoimmune and malignant pericarditis.

Drug treatment (uncomplicated, low risk, outpatient).

• Aspirin 750 to 1000 mg orally every 8 hours (maximum 4 g daily) for 1 to 2 weeks, then reduce by 250 to 500 mg every 1 to 2 weeks until stopped (total 3 to 4 weeks).
• Alternatively, ibuprofen 600 mg orally every 8 hours (maximum 2400 mg daily) for 1 to 2 weeks, reduced by 200 to 400 mg every 1 to 2 weeks.
• Continue until symptoms resolve and C-reactive protein is normal. Aspirin is preferred after myocardial infarction and in patients taking antiplatelet drugs. Avoid indometacin in older adults and coronary disease.
• Monitor creatinine, blood pressure and gastrointestinal bleeding. Avoid or use with great caution in heart failure with reduced ejection fraction, eGFR under 30 mL/min/1.73 m2, peptic ulcer disease and anticoagulant use.
• Omeprazole 20 mg orally once daily throughout NSAID therapy.
• Colchicine 0.5 mg orally once daily (weight under 70 kg) or 0.5 mg twice daily (weight 70 kg or over), without a loading dose, for 3 months. It halves recurrence and improves symptom resolution.
• Check creatinine, liver tests and creatine kinase at baseline and at 1 month. Reduce to 0.5 mg daily (or 0.5 mg on alternate days) when eGFR is 30 to 50 mL/min/1.73 m2, and avoid at eGFR under 30 or severe hepatic impairment.
• Avoid strong CYP3A4 or P-glycoprotein inhibitors (clarithromycin, ketoconazole, itraconazole, ciclosporin; reduce the dose with verapamil or diltiazem). Stop for diarrhoea, myopathy or cytopenia.
• Corticosteroids are avoided as first line therapy because they increase recurrence.
• If NSAIDs and colchicine are contraindicated or fail: prednisolone 0.2 to 0.5 mg/kg orally daily, tapered slowly, after excluding tuberculosis. Above 50 mg decrease by 10 mg every 1 to 2 weeks; 25 to 50 mg by 5 to 10 mg; 15 to 25 mg by 2.5 mg every 2 to 4 weeks; under 15 mg by 1.25 to 2.5 mg every 2 to 6 weeks.
• No routine antiviral treatment. Treat specific infections: HIV with antiretroviral therapy; cytomegalovirus in the immunosuppressed with ganciclovir 5 mg/kg intravenously every 12 hours (adjust to creatinine clearance; monitor full blood count).

Activity. Restrict physical activity until symptoms resolve and C-reactive protein is normal (non-athletes). Athletes should avoid competitive sport for at least 3 months, with return when symptoms are absent and C-reactive protein, ECG and echocardiography are normal.

Admission criteria. Any high risk feature (fever over 38 degrees Celsius, subacute onset, large effusion, failure to respond to NSAIDs after 7 days, immunosuppression, oral anticoagulation or trauma). Inpatient care for tamponade, myopericarditis with arrhythmia or ventricular dysfunction, and suspected bacterial or tuberculous pericarditis.

Myopericarditis. Treat with ibuprofen 600 mg orally every 8 hours (maximum 2400 mg daily) or aspirin 750 to 1000 mg every 8 hours at the lowest effective dose. Add colchicine 0.5 mg once or twice daily by weight for 3 months, with serial troponin, echocardiography and ambulatory ECG. Avoid NSAIDs when ejection fraction is reduced.

Give heart failure therapy for ventricular dysfunction:

• Ramipril 2.5 mg daily titrated to 10 mg.
• Bisoprolol 1.25 mg daily titrated to 10 mg.
• Spironolactone 25 to 50 mg daily (potassium under 5.0 mmol/L, eGFR over 30).

Check potassium and creatinine at 1 to 2 weeks. Avoid strenuous exercise for 3 to 6 months. Cardiac MRI at 3 to 6 months where a persistent abnormality is suspected.

Tamponade. Urgent pericardiocentesis under echocardiographic control, with a pigtail drain left until output falls under 25 mL in 24 hours, and fluid sent for cell count, biochemistry, culture, Xpert and adenosine deaminase (over 40 U/L suggests tuberculosis), and cytology. Avoid diuretics and vasodilators, and avoid intubation and positive pressure ventilation where possible.

Recurrent pericarditis (symptom recurrence after a symptom free interval of 4 to 6 weeks). Restart NSAID at full dose with colchicine for at least 6 months, with slower tapering.

For multiple recurrences, anakinra 100 mg subcutaneously once daily (reduce to 100 mg on alternate days in eGFR under 30 mL/min/1.73 m2; monitor neutrophils and liver tests; screen for tuberculosis first), or rilonacept 320 mg subcutaneously then 160 mg weekly where licensed. Constrictive pericarditis is treated with diuretics, anti-inflammatory therapy for transient constriction, and pericardiectomy for permanent constriction.

Monitoring.

• Symptoms, C-reactive protein and ECG at 1 to 2 weeks and at 4 to 6 weeks.
• Echocardiography at 1 to 2 weeks and at 3 months where an effusion was present.
• Creatinine and liver tests on colchicine.
• Follow up at 6 and 12 months for recurrence and constriction.

Referral and escalation. Refer to cardiology when any high risk feature is present, effusion is moderate or larger, or there is no response to 1 week of NSAIDs. Refer urgently for tamponade, myopericarditis with arrhythmia or ventricular dysfunction, haemodynamic compromise, suspected bacterial or tuberculous pericarditis, or recurrence despite colchicine. Refer recurrent disease to a pericardial disease or specialist cardiology service.

Special groups.

• Pregnancy: ibuprofen or aspirin up to week 20 only (avoid NSAIDs after week 20 because of foetal ductal closure and oligohydramnios); prednisolone 5 to 20 mg daily is acceptable when needed; colchicine is avoided where alternatives exist.
• Breastfeeding: ibuprofen and prednisolone are acceptable; colchicine at 0.5 mg once or twice daily is considered compatible on limited data; avoid aspirin.
• Children: ibuprofen 10 mg/kg orally every 6 to 8 hours (maximum 2400 mg daily); avoid aspirin in viral illness (Reye syndrome risk); colchicine dosing by a paediatric specialist.
• Older adults and kidney impairment: avoid or minimise NSAIDs; use colchicine at reduced doses by eGFR.
• Region specific: tuberculosis and HIV are leading causes of pericardial disease in sub-Saharan Africa, so test for both in every patient, and do not start corticosteroids before tuberculosis has been excluded.