Despite an ever-expanding array of diagnostic techniques, the vast majority of cases of pericarditis remain idiopathic in etiology [10,11,12]. Even when pericardial fluid or tissue samples are obtained, the cause is undefined in up to 30% of patients.
Broadly speaking, pericarditis is either infectious (two-thirds of cases) or noninfectious (one-third of cases) in etiology, with noninfectious cases attributable to one of a number of immune, neoplastic, traumatic, and metabolic conditions (see Table 35.1). A wide range of organisms cause infectious pericarditis, but viral infection remains the most common probable or identifiable cause. Organisms responsible for myocarditis are commonly implicated, particularly enteroviruses, adenoviruses, and influenza; herpes simplex and cytomegalovirus may also be important in immunocompromised individuals. Myopericarditis has also been reported after smallpox vaccination in US military personnel not previously exposed to vaccinia [13]. Although pericardial abnormalities are seen in up to 20% of patients with human immunodeficiency virus (HIV) infection, symptomatic pericarditis in these patients is commonly due to secondary infection (e.g., mycobacterial) or neoplasia (particularly lymphoma or Kaposi’s sarcoma), and the frequency decreases with effective antiretroviral therapy [14]. Bacterial pathogens typically cause purulent pericarditis, but are implicated infrequently in pericardial disease, typically as a consequence of hematogenous seeding or direct extension from adjacent infected tissues (lungs or pleural space) [15]. Mycobacterium tuberculosis causes up to 4% of acute pericarditis cases and 7% of tamponade presentations in developed countries, and remains an important causal factor in developing nations and immunocompromised hosts [16,17]. Tuberculosis-related pericarditis can require pericardial biopsy for diagnosis and is complicated by pericardial effusion or constriction in up to 50% of cases [18].

In the remainder of patients, pericarditis occurs in conjunction with a dissecting aortic aneurysm (in which blood leaks into the pericardial space), after blunt or sharp trauma to the chest, as a result of neoplastic invasion of the pericardium, after chest irradiation, in association with uremia or dialysis, after cardiac or other thoracic surgery, in association with an inflammatory or autoimmune disorder, or as a result of certain pharmacologic agents. Iatrogenic cases are increasingly common, with postpericardiotomy syndrome reported in up to 20% of patients at a median of 4 weeks following cardiac surgery [19] and symptomatic pericarditis in up to 2% of patients undergoing percutaneous coronary intervention, catheter ablation procedures, or implantation of active fixation pacemaker or defibrillator leads [10]. Pericarditis associated with acute transmural myocardial infarction and the delayed immune-mediated postinfarction pericarditis of Dressler’s syndrome used to be common, but the incidence has declined with the broader utilization of early reperfusion strategies for acute coronary syndromes (thrombolysis and primary angioplasty).

Although patients with acute pericarditis may be asymptomatic, the typical presentation is with chest pain that is retrosternal in location, sudden in onset, and exacerbated by inspiration (pleuritic). The pain may be made worse by lying supine and improved by sitting upright and leaning forward. Precordial distress may closely mimic angina, including a predominant pressure sensation with radiation to the neck, arms, or left shoulder. However, radiation of chest pain to one or both trapezius muscle ridges favors the diagnosis of pericarditis because the phrenic nerve, which innervates these muscles, traverses the pericardium. A prodrome of low-grade fever, malaise, and myalgia is common, but fever may be absent in elderly patients. Associated symptoms can include dyspnea, cough, anorexia, anxiety, and occasionally, odynophagia or hiccups.

Nearly 85% of patients with pericarditis have an audible friction rub during the course of their disease [12]. Typically, the rub is a high-pitched scratchy or squeaky sound best heard at the lower left sternal border or apex at end expiration with the patient leaning forward. Classically, it consists of three components corresponding to ventricular systole, early diastolic filling, and atrial contraction, and has been likened to the sound made when walking on crunchy snow. It is distinct from a pleural rub in that it is present throughout the respiratory cycle, whereas the pleural rub disappears when respirations are suspended. The pericardial friction rub is often a dynamic sound that can disappear and reappear over short periods of time. Because of this variable quality, frequent auscultation in the upright, supine, and left lateral decubitus positions is important for patients in whom a diagnosis of pericarditis is suspected.

The electrocardiogram (ECG) is a key diagnostic test in suspected pericarditis, though typical changes are not always seen. The classic finding is widespread, concave ST-segment elevation, often with associated PR-segment depression (Fig. 35.2). Although the changes may appear regional and therefore mimic myocardial ischemia, reciprocal ST-segment depressions are absent, as are pathologic Q-waves. In addition, the ECG in pericarditis exhibits a typical pattern of evolution that is
distinct from that of patients with evolving myocardial infarction. In patients with pericarditis, the ECG on presentation usually demonstrates diffuse ST-segment elevation and PR-segment depression (stage I) and evolves through three subsequent phases [20]. During the evolutionary phase (stage II), all ST-junctions return to baseline more or less “in phase,” with little change in T-waves. (By contrast, in patients with ST-segment elevation due to acute myocardial injury, T-wave inversion begins to occur before the ST-segments return to baseline.) The T-waves subsequently flatten and invert (stage III) in all or most of the leads that showed ST-segment elevations. In stage IV, the T-waves return to their prepericarditic condition. The widespread T-wave inversions that appear in stage III are indistinguishable from those of diffuse myocardial injury, myocarditis, or biventricular injury. The entire ECG evolution occurs in a matter of days or weeks, but may not be seen in every patient. Often, the transition from stage III to stage IV is relatively slow, with some patients left with some degree of T-wave inversion for an indefinite period.

Although some 80% of patients with pericarditis exhibit a typical stage I ECG during their course [21], atypical variants (or even a normal ECG) may also be seen. An important ECG variant that can be quasidiagnostic is PR-segment (not PR-interval) depression in the absence of true ST-segment elevation, which though nonspecific, may be the only sign of pericarditis. This may occur as a consequence of superficial myocarditis affecting the atrium [22]. Although the ST-changes of pericarditis may occasionally resemble those of normal early
repolarization, a useful differentiating feature may be the ratio between the height of the ST-segment and the T-wave in lead V₆. A ratio exceeding 0.24 favors the diagnosis of pericarditis [23].

Although laboratory findings in patients with suspected pericarditis are nonspecific, measurement of serum markers of inflammation (leukocyte count, erythrocyte sedimentation rate, C-reactive protein, and lactate dehydrogenase) and myocardial necrosis (creatine kinase, and troponins) may help to establish or confirm the diagnosis, define the extent of associated myocardial injury, and guide subsequent follow-up. The 2004 European Society of Cardiology guidelines on the management of pericardial diseases [24] therefore advise measurement of these parameters as part of the initial diagnostic evaluation in all patients, but this recommendation remains somewhat controversial. A markedly elevated white blood cell count, particularly in association with high fever, should raise suspicion for purulent pericarditis, and may prompt sampling of pericardial fluid (if present) for diagnosis. Cardiac enzymes including creatine kinase (creatine kinase, total and MB-fraction) and troponins are commonly elevated in patients with pericarditis due to associated epicardial inflammation or myocarditis [25]. Elevations in troponin I are seen more commonly than those in CK-MB and are frequently associated with male gender, ST-segment elevation, younger age at presentation, and pericardial effusion. The degree of troponin elevation is roughly related to the extent of myocardial inflammation and, distinct from acute coronary syndromes, does not appear to correlate with long-term prognosis [26]. Routine measurement of cardiac troponins in patients with suspected or definite pericarditis may therefore be unnecessary, unless there is suspicion for associated transmural myocardial infarction by ECG (due to the presence of pathologic Q-waves) [27]. Similarly, routine serologic testing for antinuclear antibodies or rheumatoid factor is rarely helpful, save in those patients in whom other clinical features suggest underlying connective tissue illness.

The chest radiograph is typically normal in acute pericarditis, but is often performed as a matter of course to assess for abnormalities in the mediastinum or lung fields, which may suggest an etiology, and to exclude cardiomegaly, which suggests the presence of a substantial pericardial effusion (> 250 mL). Pericardial calcification is rarely seen, but may suggest constrictive pericarditis. Any suspicion for cardiomegaly should prompt a transthoracic echocardiogram to assess for hemodynamically significant pericardial effusion or tamponade. Routine echocardiography in patients with unequivocal evidence of pericarditis and normal hemodynamics by physical examination is probably unnecessary, though the detection of a pericardial effusion may help to support the diagnosis. In addition, detection of wall motion abnormalities or left ventricular dysfunction on echocardiography may be helpful in detecting associated myocardial infarction or in assessing the severity of associated myocarditis.

There are no large, randomized, controlled clinical trials to guide the therapy of patients with acute pericarditis. Initial management is directed at screening for specific etiologies and underlying conditions that may alter the treatment strategy (e.g., connective tissue disease, HIV infection, and tuberculosis) and control of symptoms. In the vast majority of patients, acute idiopathic pericarditis is a self-limited disease without significant complications or recurrence, and may be safely managed in the outpatient setting [28]. A subset of patients with high-risk features including fever greater than 38°C, subacute course (symptoms developing over days or weeks), large pericardial effusion (> 20 mm in width in diastole by echocardiography), cardiac tamponade, or failure to respond to treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered for hospital admission to permit additional observation and a more extensive etiologic work-up [29]. Immunosuppressed patients and those with blunt or penetrating chest trauma, serologic evidence of myocarditis (based on elevated cardiac biomarkers), or need for oral anticoagulant therapy may also be at risk for complications and warrant closer observation [30].

Treatment of pericarditis may vary on the basis of etiology. For the minority of cases in which a specific diagnosis is identified, therapy should be tailored appropriately, as outlined in
Table 35.1. (Details of treatment for specific conditions are beyond the scope of this discussion.) In uncomplicated cases of idiopathic pericarditis, treatment with NSAIDs is the cornerstone of therapy. Across the board, these agents are effective in reducing inflammation and symptoms of pain, fever, and malaise associated with pericarditis. Limited observational data suggest that the various available NSAIDs have comparable efficacy [31]. As a first-line agent, many favor treatment with ibuprofen, which is well tolerated and can easily be titrated over a range of doses. The typical dose is 600 mg every 6 hours, which sometimes relieves pain within 15 minutes to 2 hours of the first dose. Depending on patient tolerance and therapeutic response, the individual dose can be reduced to 400 mg or raised to 800 mg or greater with continued observation for side effects. Should this fail, aspirin 600 to 900 mg four times per day may be given. Indomethacin may be used, always given on a full stomach and in divided doses from 100 to 200 mg per day, beginning with 25 mg every 6 hours. In patients with myocardial infarction–related pericarditis, indomethacin should probably be avoided in light of experimental work showing that it reduces coronary flow, increases experimental infarction size, and raises blood pressure. Aspirin is the agent of choice in these cases because among the NSAIDs, it least retards scar formation in the infracted heart [32]. In all patients receiving high-dose NSAIDs, gastrointestinal protection with an antacid or proton–pump inhibitor should be considered to reduce the risk of drug-induced gastritis or bleeding.