In North America and western Europe (countries with a low prevalence of tuberculosis), acute pericarditis is most often idiopathic (80%-55% of unselected cases) and is typically a self-limited disease usually lasting 2 to 6 weeks. Small pericardial effusions occur commonly (up to 60% of cases), but cardiac tamponade is unusual (< 5% of cases). Heart failure caused by associated myocarditis and constrictive pericarditis is uncommon. These complications usually can be detected by clinical and echocardiographic evaluation. The clinical course and prognosis of individuals with pericarditis are otherwise largely determined by the presence and nature of any underlying disease.
Viral pericarditis is the most common infectious type, although a definitive diagnosis from acute and convalescent (3 weeks) viral neutralizing antibodies is generally not helpful in a sporadic case of pericarditis. Viral isolation from pericardial fluid and in situ hybridization techniques have been used to identify a specific etiology. However, viral infection is often presumed rather than proved, and many cases are classified as idiopathic. Common viral infections causing acute pericarditis are those resulting from echovirus and coxsackievirus; however, several other viruses may cause pericarditis (see Table 66–2).
However, in immunocompetent patients, there are no proven antiviral therapies to offer, and the disease is usually self-limiting and resolving, while pericardial inflammation and pain are treated by aspirin or a NSAID and colchicine. Thus, it is absolutely not necessary to reach a specific viral etiology in clinical practice.
The most common cause of bacterial (purulent) pericarditis is tuberculous pericarditis. Tuberculosis is the leading cause of pericardial diseases in developing countries and all over the world. Purulent pericarditis is now relatively rare, especially in countries with a low prevalence of tuberculosis.37
In developed countries, bacterial pericarditis is most often caused by streptococci, staphylococci, gram-negative rods, and, increasingly, anaerobic bacteria.38 Haemophilus influenzae is an important cause in children. The increasing frequency of cardiac surgery and percutaneous interventions, selection-induced changes in the flora responsible for hospital-acquired infections, and prolonged survival of immunocompromised hosts (eg, human immunodeficiency virus [HIV], steroids) have changed the incidence and bacterial spectrum of purulent pericarditis. Predisposing factors include pericardial effusion, immunosuppression, chronic diseases (eg, alcohol abuse, rheumatoid arthritis, chronic kidney disease, malignancy), cardiac surgery, and chest trauma. Pericardial involvement often is unrecognized when it complicates systemic infection; unusually high fever and high white blood cell counts are clues to the presence of pericarditis. Children and immunosuppressed patients of all ages are most vulnerable, and the characteristic features of acute pericarditis are frequently absent. The course of bacterial pericarditis is fulminant, often presenting with cardiac tamponade; adhesive and constrictive pericarditis are common sequelae in survivors and may develop suddenly and early. Less common complications of purulent pericarditis include mycotic aneurysms (most often Staphylococcus and Salmonella species in the thoracic aorta) and left ventricular and submitral pseudoaneurysms.38 Pericarditis complicating systemic infection and sepsis may go unrecognized and misdiagnosed. Many patients lack the typical findings of pericarditis, and the diagnosis of purulent pericarditis often is made either at autopsy or after cardiac tamponade develops; empyema is a common antecedent. The threshold for echocardiography in the septic patient should be low, and whenever purulent pericarditis is suspected, the pericardial space should be explored and fluid and blood sent for extensive microbiologic testing. Bacterial pericarditis is treated with surgical exploration and drainage and appropriate systemic antibiotics. Fibrinolytics may be used to lyse fibrous adhesions, liquefy purulent exudate, and prevent constrictive pericarditis. Pericardiectomy may be required for dense adhesions, loculated and thick effusions, persistent infection, recurrence of tamponade, and constriction. Although fatal if untreated, mortality remains high (~40%) in those receiving proper therapy.37,38
Legionella infections account for approximately 10% of community-acquired pneumonias and may be associated with pericarditis more often than previously was appreciated. Studies suggest that patients with pericardial involvement tend to be younger and healthier than those without it. Recurrent pericarditis, effusion, and chronic constriction occur in approximately 20% to 30% of cases.27 Pericarditis may be an early complication of Lyme disease.
Tuberculosis is a major cause of pericarditis in nonindustrialized countries, but an uncommon cause in developed countries with a low prevalence of tuberculosis.1 Nevertheless, its incidence is increasing because of HIV infection; consequently, tuberculosis should be considered in the differential diagnosis of pericardial heart disease.1,39
Tuberculous pericarditis results from hematogenous spread of primary tuberculosis or from the breakdown of infected mediastinal lymph nodes, with the result that affected individuals generally lack the typical symptoms and signs of pulmonary tuberculosis. A delayed hypersensitivity response to protein antigens of the bacilli that penetrate the pericardium is responsible for the morbidity associated with tuberculous pericarditis.
Fever, weight loss, and night sweats occur early; pericardial pain and friction rubs are often absent. Enlargement of mediastinal lymph nodes is not routinely seen on chest radiography (CT or magnetic resonance imaging [MRI] is required), although an enlarged cardiac silhouette is common. Patients may present with tamponade or constriction, which may be subacute. A fibrinous pericarditis with caseating necrosis and mononuclear infiltrate gives rise to an effusive phase, which is often voluminous and hemodynamically significant. An adhesive phase follows resolution of the effusion and eventuates in dense, calcific adhesions with clinical constriction in > 30% of patients.1,39
A definite diagnosis of tuberculous pericarditis is based on the demonstration of the presence of tubercle bacilli in the pericardial fluid or tissue. However, a probable diagnosis of tuberculous pericarditis can be achieved with evidence of the disease elsewhere (eg, pulmonary tuberculosis) and concomitant pericarditis, a lymphocytic pericardial exudate with elevated unstimulated interferon-gamma, adenosine deaminase, or lysozyme levels. An ex juvantibus diagnosis is admitted only in countries with a high prevalence of tuberculosis with the demonstration of the response to empiric antituberculous therapy.1,39,40 A presumptive diagnosis generally requires a history of contact and/or purified protein derivative conversion (although the latter lacks sensitivity and specificity).
A regimen consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol for at least 2 months, followed by isoniazid and rifampicin (total of 6 months of therapy), is effective in treating extrapulmonary tuberculosis. Treatment for 9 months or longer gives no better results and has the disadvantages of increased cost and increased risk of poor compliance. Tuberculous pericarditis has a high risk of evolving in constrictive pericarditis, usually within 6 months in effusive forms. Prompt antibiotic therapy is essential to prevent this progression, which occurs in 20% (especially in developed countries) to 40% of cases. Additional treatments that may be useful to prevent constriction include intrapericardial urokinase and adjunctive prednisolone for 6 weeks, which may halve this complication (to be avoided in HIV-infected patients because it increase the risk of HIV-associated malignancies).1,39,40,41
Pericardiectomy is recommended if the patient’s condition is not improving or is deteriorating after 4 to 8 weeks of antituberculosis therapy (Class I recommendation; LOE: C).1
Human Immunodeficiency Virus Pericarditis
HIV is an important cause of pericardial heart disease. The presence of pericardial effusion was considered a negative prognostic predictor in past years. However, today, patients with HIV who are treated with highly active antiretroviral therapies (HAART) may have an etiologic spectrum of pericardial diseases that is similar to that of a non–HIV-infected population.42
Pericardial involvement may be a result of associated malignancies (eg, lymphoma and Kaposi sarcoma), viruses (including HIV), and opportunistic infections (eg, mycobacteria, cytomegalovirus, Nocardia, and cryptococci) and, irrespective of its cause, predicts a poor prognosis in patients with HIV infection if they are not treated by HAART. Large symptomatic pericardial effusion in patients with HIV infection should be aggressively investigated because two-thirds of these cases have an identifiable cause. Tamponade in patients with HIV is mycobacterial (Mycobacterium tuberculosis or Mycobacterium avium-intracellulare) in origin in approximately one-third of patients.42 Tuberculous pericarditis in those with HIV infection is associated with a lower risk of constriction.1
Neoplastic pericardial involvement is manifested by pericarditis or simple pericardial effusion (usually moderate to large, cardiac tamponade) related to metastatic lymphatic involvement (especially for lung cancer) or hematogenous spread (especially for breast cancer). In addition, lymphomas, leukemias, melanoma, and cancer of contiguous organs (eg, esophageal cancer) may also affect the pericardium. Only rarely is neoplastic disease primary (usually pericardial mesothelioma).1,43,44,45
Neoplastic pericardial disease may be manifested as pericarditis, pericardial effusion, effusive-constrictive pericarditis, or constrictive pericarditis. Masses may be diagnosed by imaging techniques.
The definite diagnosis is based on the confirmation of the malignant infiltration within the pericardium by cytology or pericardial biopsy. A probable diagnosis may be achieved by the detection of tumor markers in pericardial fluid (eg, carcinoembryonic antigen [CEA], cytokeratin 19 fragment [CYFRA 21-1]), although none of the tumor markers has been proven to be accurate enough for distinguishing malignant from benign effusions. Evidence of malignant disease elsewhere and concomitant pericarditis or pericardial effusion are also suggestive, although in almost two-thirds of patients with documented malignancy, pericardial effusion is caused by nonmalignant diseases (eg, radiation pericarditis, other therapies, opportunistic infections). The management of these patients require a multidisciplinary approach with oncologists, radiotherapists, and other subspecialty experts.43
Pericardial Diseases in Systemic Inflammatory Diseases and Post–Cardiac Injury Syndromes
Systemic inflammatory diseases (especially systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, scleroderma, systemic vasculitides, Behçet syndrome, sarcoidosis, and inflammatory bowel diseases) are common causes of pericarditis or “apparently” isolated pericardial effusion. Up to 10% of patients with pericarditis (often recurrent) have a known systemic inflammatory disease, but rarely, pericarditis/pericardial effusion may be the first manifestation of the systemic disease. Usually the degree of pericardial involvement is related to the activity of the systemic disease. Moreover, concomitant myocarditis may be present as well, because it is also a cause of myocardial inflammatory involvement.43,46
A specific subgroup of these patients, especially children, may be affected by periodic fevers or autoinflammatory diseases. Periodic fevers are genetic disorders characterized by mutations of genes involved in the regulation of the inflammatory response, without involvement of specific T cells or autoantibodies. The most common autoinflammatory syndromes include familial Mediterranean fever, in which serositis episodes last only 1 to 3 days, and tumor necrosis factor receptor–associated periodic syndrome, in which the episodes last weeks. Mutations associated with these disorders are rare in recurrent pericarditis. A positive family history for pericarditis or periodic fevers, a poor response to colchicine, and the need for immunosuppressive agents are clues to the possible presence of an autoinflammatory disease. Genetic testing is required for the definitive diagnosis.43
The term post–cardiac injury syndromes includes a group of inflammatory pericardial syndromes (post–myocardial infarction pericarditis, post-pericardiotomy syndrome, and post–traumatic pericarditis). Such syndromes are presumed to have an autoimmune pathogenesis triggered by an initial damage to pericardial and/or pleural tissues, caused by either myocardial necrosis (late post–myocardial infarction pericarditis or Dressler syndrome), surgical trauma (post-pericardiotomy syndrome), accidental thoracic trauma (traumatic pericarditis), or iatrogenic trauma with or without bleeding (pericarditis after invasive cardiac interventions).2,47 Such forms are increasing, especially in developed countries, as a result of the aging of the population and the widespread use of percutaneous coronary intervention.
Treatment of these forms is similar to that of idiopathic pericarditis, with use of aspirin/NSAID plus colchicine as a first-line therapy and corticosteroids as a valid option especially when patients are on oral anticoagulants and interaction with anti-inflammatory drugs is not wanted.43,47
Radiation-Induced Pericardial Disease
Prior chest radiation is an important cause of pericardial disease. Radiation therapy may affect not only the pericardium, but also the myocardium, heart valves, coronary arteries, and all mediastinal structures inducing fibrosis. Most cases are secondary to radiation therapy for Hodgkin lymphoma or breast or lung cancer, and serious radiation-induced pericardial disease is most often a result of radiation therapy of Hodgkin lymphoma. Today, lower doses and modern radiation therapy (shielding and dose calculation) have reduced the complications; radiation pericarditis has now dropped from 20% to 2.5% of cases.
Radiation can induce an early disease, with pericarditis with or without effusion, and a late disease, with constrictive pericarditis after 2 to 20 years and not necessarily preceded by pericarditis. This late disease may affect a variable number of patients (4%-20% of patients) and appears to be dose dependent and related to the presence of late pericardial effusion in the delayed acute phase. The effusion may be serous or hemorrhagic and has a high probability to develop fibrous adhesions. Therapies are similar to those employed in pericarditis and pericardial effusion.
The concomitant possible myocardial damage affects the prognosis because radiation-induced constrictive pericarditis has a worse outcome after pericardiectomy.1,43,48
Traumatic Pericardial Disease
Blunt and penetrating traumas are important causes of pericarditis, particularly among young men. Acute tamponade beginning very soon after trauma (pericardial injury syndrome), recurrent pericardial effusion, recurrent acute pericarditis (postpericardial syndrome), and chronic constrictive pericarditis are well-recognized complications.
Severe blunt trauma, as with a fall from a considerable height, can rupture the pericardium, resulting in the potentially fatal complication of herniation of the heart. This event should be suspected if the chest radiography shows pneumothorax or air in the mediastinum distributed between the heart and diaphragm.
The application of echocardiography in the trauma unit rapidly and accurately diagnoses hemopericardium in patients with potentially penetrating cardiac wounds. Failure to repair the injury responsible for tamponade is associated with a poor clinical outcome. Constrictive pericarditis may be delayed, presenting weeks or years after the injury.
Chylopericardium is a milky-white pericardial effusion comprised of chyle, the normal content of the lacteals (lymphatics of the small intestine) and thoracic duct; the composition is variable, but generally has a high content of chylomicrons, protein, and lymphocytes. The disorder is rare, but morbidity (a result of nutritional, metabolic, and immunologic abnormalities) and mortality are considerable. Although the majority of cases are asymptomatic, cardiac tamponade can occur. Acute pericarditis and chronic constriction may result from the irritant effects of chyle.
Chylous pericardial effusions generally follow traumatic (blunt or penetrating) or surgical injury (thoracic or cardiac) to the thoracic duct, but may result from neoplastic obstruction of the duct (secondary chylopericardium); less commonly, they may be idiopathic (primary). Drainage and dietary manipulation are effective in approximately 55% of cases. Failure to respond to a diet rich in medium-chain triglycerides and pericardiocentesis warrants ligation of the thoracic duct and pericardiectomy. In cases deemed inappropriate for aggressive therapy, implantation of a valved pericardioperitoneal conduit has been helpful.
Pericardial Diseases in Renal Failure
Pericardial diseases in renal failure have been become less common than in the past, but should be considered in the differential diagnoses for pericarditis and pericardial effusion. There are three main presentations of pericarditis in renal failure: (1) uremic pericarditis, occurring before renal replacement therapy or within 8 weeks from its initiation and related to retention of toxic metabolites; (2) dialysis pericarditis, occurring on dialysis (usually ≥ 8 weeks after its initiation); and (3) constrictive pericarditis, occurring only rarely.1,4,49,50
Myxedema Pericardial Disease
Pericarditis with effusion (sometimes containing cholesterol) occurs in approximately one-third of patients with myxedema. Effusions develop slowly and may reach a prodigious size; slow resolution usually follows the institution of thyroid replacement therapy. Pericardial drainage is generally not indicated because myxedema effusions seldom cause tamponade.1