The diagnosis of acute pericarditis relies on clinical findings, ECG changes, and echocardiography (table 1).2,3
Chronic pericardial inflammation includes effusive, adhesive, and constrictive forms, lasting three months or more. Recurrent pericarditis may be intermittent (symptom-free interval without treatment) or incessant (discontinuation of anti-inflammatory treatment always ensures a relapse).
Table 1 Diagnostic pathway and sequence of performance in acute pericarditis.2,3
Pericardial effusion occurs as transudate (hydropericardium), exudate, pyopericardium or haemopericardium, or a mixture of these. Large effusions generally indicate more serious disease and are common with neoplasia, tuberculosis, hypercholesterolaemia, uraemic pericarditis, myxoedema, and parasitoses.2,4
Patients can be asymptomatic if effusion develops slowly. Many pregnant women develop a minimal to moderate clinically silent hydropericardium by the third trimester. Fetal pericardial fluid can be detected by echocardiography after 20 weeks’ gestation and is normally 2 mm or less in depth. More fluid should raise questions of hydrops fetalis, Rh disease, hypoalbuminaemia, and immunopathy or maternally transmitted mycoplasmal or other infections, and neoplasia.3
Echocardiography reveals the size of effusions: (1) small (echo-free space in diastole < 10 mm); (2) moderate (at least
10 mm posteriorly); (3) large (
20 mm); or (4) very large (
20 mm with compression of the heart).2
Presence of fibrin, clot, tumour, air, and calcium can also be detected. Pericardial effusion must be differentiated from pleural fluid, ascites, atelectasis, or epicardial fat. Transoesophageal echocardiography is useful in loculated pericardial effusions, intrapericardial clots, metastases, and pericardial thickening.
Cardiac tamponade is a medical emergency and its diagnosis is of major clinical importance (table 2).3
Pericardial disease of almost any aetiology can produce cardiac tamponade by effusion accumulation and increased intrapericardial pressure. “Surgical tamponade” (for example, haemorrhage) can quickly overwhelm compensatory mechanisms. Slowly developing “medical tamponade” may first appear with an effusion of 500–2000 ml.
Constrictive pericarditis causes impaired filling of the ventricles and reduced ventricular function (table 3).3,5
Tuberculosis, mediastinal irradiation, and previous cardiac surgery are frequent causes. Differential diagnosis must include pulmonary embolism, right ventricular infarction, pleural effusion, chronic obstructive lung disease, and restrictive cardiomyopathy. The best way to distinguish constrictive pericarditis from restrictive cardiomyopathy is by analysing respiratory and preload changes using Doppler/tissue Doppler echocardiography.3
Physical findings, ECG, chest radiography, computed tomography/magnetic resonance imaging (CT/MRI), haemodynamics, and endomyocardial biopsy may be helpful as well.
Table 3 Diagnostic approach in constrictive pericarditis3,5
How to establish the aetiology?
Viral pericarditis is the most common infectious disease of the pericardium and is caused by direct viral attack (enterovirus, adenovirus, cytomegalovirus (CMV), Ebstein-Barr virus, herpes simplex virus, influenza virus, parvo B19, hepatitis C virus, HIV, etc), the immune response, or both.6
Initial presentation is most frequently the syndrome of acute pericarditis, often resolving within two weeks, but with up to 50% recurring.3
The acute effusive form, particularly after tamponade, is associated with constriction more often than “dry” pericarditis. Arrhythmias or conduction defects indicate myocarditis or other concomitant heart disease. Diagnosis is not possible without the evaluation of pericardial effusion and/or pericardial/epicardial tissue by polymerase chain reaction (PCR) or in situ hybridisation (fig 1). A fourfold rise in serum antiviral antibodies is suggestive but not diagnostic per se.
Viral pericarditis: (A) pericardioscopy findings; (B) epicardial in situ hybridisation positive for cytomegalovirus; (C) cytology of pericardial effusion; (D) epicardial immunofluorescence staining.
The diagnosis of autoreactive pericarditis is established by: (1) an increased number of lymphocytes/mononuclear cells > 5000/mm3
(autoreactive lymphocytic), or the presence of antibodies against heart muscle tissue in the pericardial fluid (autoreactive antibody mediated); (2) signs of myocarditis on epicardial/endomyocardial biopsies (
); (3) exclusion of active viral infection in pericardial effusion and endomyocardial/epimyocardial biopsies (no virus isolation, no immunoglobulin IgM titre against cardiotropic viruses in pericardial effusion, and negative PCR for major cardiotropic viruses); (4) tuberculosis, Borrelia burgdorferi
, Chlamydia pneumoniae
, and other bacterial infection excluded by PCR and/or cultures; (5) no neoplastic infiltration in pericardial effusion or tissue; and (6) exclusion of uraemia, systemic, and metabolic disorders.7
Despite treatment, purulent pericarditis is fatal in up to 40% of patients (tamponade, toxicity, constriction). Predisposing conditions are pre-existing pericardial effusion, immunosuppression, and chronic diseases (alcoholism, rheumatoid arthritis, etc). Pericardial fluid should undergo urgent Gram, acid-fast, and fungal staining, followed by cultures for aerobes and anaerobes of the pericardial and body fluids. Purulent effusions have significantly lower fluid glucose concentrations (mean (SD) 47.3 (25.3) v
102.5 (35.6) mg/dl) and fluid to serum ratios (0.28 (0.14) v
0.84 (0.23) mg/dl), than non-infectious effusions.8
In the last decade tuberculous pericarditis in developed countries has been primarily seen in immunocompromised patients (AIDS).9
Pericardial constriction occurs in 30–50% of cases and mortality in untreated disease approaches 85%. The absolute criteria for diagnosis are the identification of Mycobacterium tuberculosis
in the pericardial fluid or tissue, and/or the presence of caseous granulomas in the pericardium.3
However, pericarditis in proven extracardiac tuberculosis is strongly suggestive of a tuberculous aetiology. A systematic, multiple diagnostic approach is essential (sputum cultures, ELISPOT skin test, analyses of pericardial effusion by acid-fast staining, mycobacterial culture or radiometric growth detection (for example, BACTEC-460), adenosine deaminase (ADA), pericardial lysozyme, and PCR for M tuberculosis
High ADA (> 40 U/l) in pericardial effusion is diagnostic for tuberculous pericarditis (93% sensitivity, 97% specificity) and prognostic for pericardial constriction.11
PCR is as sensitive (75% v
83%), but more specific (100% v
78%) for tuberculous pericarditis than ADA. Both pericardioscopy and pericardial biopsy have further improved the diagnostic accuracy for tuberculous pericarditis.12
Two forms of pericarditis have been described in renal failure:
- Uraemic pericarditis—fibrinous inflammation with adhesions between the thickened pericardial membranes (“bread and butter” appearance) caused by the high degree of azotemia (blood urea nitrogen usually > 60 mg/dl) in advanced renal failure before dialysis is started or shortly thereafter.
- Dialysis associated pericarditis—patients on maintenance haemodialysis, and occasionally with chronic peritoneal dialysis caused by inadequate dialysis and/or fluid overload.
After renal transplantation pericarditis may be caused by uraemia or infections (for example, CMV).
The post-cardiac injury syndrome develops within days to months after cardiac/pericardial injury. Unlike the post-myocardial infarction syndrome, it acutely provokes a greater antiheart antibody response (antisarcolemmal and antifibrillary). These antibodies appear to be pathogenic or may act in the presence of a dormant or concurrent viral infection.
Pericarditis may occur “early” (pericarditis epistenocardica) or be “delayed” (Dressler’s syndrome) after myocardial infarction. Epistenocardiac pericarditis, caused by direct exudation, occurs in the first several days of almost half of transmural myocardial infarctions, although early thrombolytic treatment has decreased its incidence. Dressler’s syndrome occurs from one week to several months after myocardial infarction (also in subendocardial forms) with manifestations similar to the post-cardiac injury syndrome. Cardiac tamponade may occur relatively early. Late constriction is rare but not surprising because of intrapericardial organisation of exudate and blood that can also produce loculated effusions. If the diagnosis of acute myocardial infarction is mistaken, thrombolysis may produce tamponade from inflamed pericardium or aortic dissection.
Neoplastic pericarditis is 40 times more often caused by secondary than primary malignancies, most frequently by lung cancer, breast cancer, malignant melanoma, lymphomas, and leukemias. Effusions may be small or large with an imminent tamponade or constriction. The diagnosis is based on pericardial fluid cytology and pericardial/epicardial biopsy findings (fig 2). CT/MRI can reveal localisation of the primary tumour or the metastases. Pericardial fluid cytology is positive in 75–87% and pericardial biopsy in 27–65% of patients with malignant pericardial disease.13
However, pericardial biopsies guided by pericardioscopy have a diagnostic value of 93.3–97%.12,14
Increased concentrations of specific tumour markers (for example, carcinoembryonic antigen (CEA), α-feto protein (AFP), carbohydrate antigens CA 125, CA 72-4, CA 15-3, CA 19-9, CD-30, CD-25) may also suggest the diagnosis. Of note, in 60% of the patients with documented malignancy, pericardial effusion is caused by non-malignant diseases—for example, radiation pericarditis or opportunistic infections.13
Neoplastic pericarditis in Hodgkin’s disease: (A) pericardioscopy findings; (B) epicardial histology; (C) cytology of pericardial effusion; (D) epicardial immunofluorescence.
Fungal pericarditis occurs mainly in immunocompromised patients (Candida
, and Actinomyces
species) or in the course of endemic fungal infections (Histoplasma
The clinical picture comprises the full spectrum of pericardial diseases including fungal myocarditis. Diagnosis is obtained by staining and culturing pericardial fluid or tissue, but antifungal antibodies in serum are also helpful.3
Chylopericardium refers to a communication between the pericardial sac and the thoracic duct caused by congenital anomalies, trauma, mediastinal lymphangiomas, lymphangiomatous hamartomas, mediastinal or pericardial lymphangiectasis, obstruction or anomalies of the thoracic duct, or caused iatrogenically during surgery. Infection, tamponade or constriction may aggravate the prognosis. The chylous nature of the fluid is confirmed by its alkaline reaction, specific gravity between 1010 and 1021, Sudan III stain for fat, and the high concentrations of triglycerides (5–50 g/l) and protein (22–60 g/l). Enhanced CT, alone or combined with lymphography, is a reliable diagnostic tool for identifying not only the location of the thoracic duct but also its lymphatic connection to the pericardium.3