PROBLEM INFECTIONS IN PRIMARY CARE

Acute pericarditis

Evaluation and treatment of infectious and other causes

Alicia M. Ross, MD; Susan E. Grauer, MD

VOL 115 / NO 3 / MARCH 2004 / POSTGRADUATE MEDICINE

CME learning objectives

• To learn the major causes of acute pericarditis and which are most common
• To recognize the clinical presentation of acute pericarditis
• To become familiar with the treatment and common complications of acute pericarditis

The authors disclose no financial interests in this article and no unlabeled uses of any product mentioned.

Fifth in a series of articles on problem infections in primary care, coordinated by Larry J. Strausbaugh, MD, hospital epidemiologist and staff physician, Veterans Affairs Medical Center, Portland, Oregon, and professor of medicine, Oregon Health & Science University School of Medicine, Portland.

Preview: Diseases of the pericardium, primarily acute pericarditis, are common in primary care. Many cases of acute pericarditis have a benign infectious origin and are self-limited. However, serious causes, including tuberculous and neoplastic diseases, should be considered. In this article, Drs Ross and Grauer highlight the more common causes to consider and review the clinical presentation, evaluation, and treatment of acute pericarditis.
Ross AM, Grauer SE. Acute pericarditis: evaluation and treatment of infectious and other causes. Postgrad Med 2004;115(3):67-75

Acute pericarditis is a syndrome caused by inflammation of the pericardium (the sac that encloses the heart and great vessels). The pericardium is composed of two layers: a fibrous outer layer called the parietal pericardium and a serous inner layer called the visceral pericardium. The two layers are attached by connective tissue and separated by up to 50 mL of pericardial fluid (1).

The pericardium functions as a barrier against infection and the spread of malignancy, limits excessive cardiac movement, and reduces friction between the heart and other organs (1,2). The intrapericardial pressure, which is normally negative, also has an important role in allowing distention of the cardiac chambers in diastole (2).

In acute pericarditis, an inflammatory response to some agent or event causes increased vascular permeability, vasodilation, and transudation of fluid into the pericardial space. Evidence of inflammation with polymorphonuclear leukocytes, fibrous deposition, and adhesions can be seen in both layers of the pericardium (1).

Causes

Acute pericarditis can result from many different causes (3-7) (table 1). Some of the more common causes are idiopathic, viral, tuberculous, and neoplastic.

Idiopathic origin
In a study by Zayas and associates (8), 100 consecutive patients who were hospitalized for acute pericarditis were evaluated according to a standardized diagnostic protocol, which included history taking, physical examination, chest radiograph, electrocardiogram (ECG), echocardiogram, and extensive laboratory evaluation. A specific cause was identified in only 22% of patients. Many experts believe that most cases of idiopathic acute pericarditis are caused by a viral infection, because no clinical or epidemiologic features have been identified that distinguish between idiopathic and viral cases (9).

Viral infection
Many viruses are associated with heart disease, including coxsackieviruses and other enteroviruses. An association has been reported between acute pericarditis and epidemics of coxsackievirus infection (9). Although identification of viruses from pericardial fluid is unusual, diagnoses have been made on the basis of isolation of a virus from other body sites or a large rise in antibody titers after acute infection (9). Because most cases of viral or idiopathic acute pericarditis are self-limited and benign, extensive diagnostic evaluations have a very low yield and generally do not change management.

Bacterial infection
Although relatively uncommon, bacterial pericarditis remains a potentially treatable and sometimes misdiagnosed cause of pericarditis. Over the past century, a marked shift has occurred in the microorganisms causing bacterial pericarditis and in the population of patients affected. In the preantibiotic era, this disease was seen primarily in young patients with pneumococcal pneumonia or other primary infections. More recently, older adults with noninfectious underlying diseases have been affected (10). The most common bacterial causes are now Staphylococcus species and various gram-negative bacilli, and most cases are associated with thoracic surgery, chronic renal failure, or malignant disease (10).

Tuberculous disease
Tuberculous pericarditis can be a challenging diagnosis in patients with acute pericarditis. Although it is usually suspected in patients who have a protracted course or large pericardial effusion, it may present in any manner and should be suspected in all patients with acute pericarditis (11).

Neoplastic disease
Pericardial involvement has been seen in up to 10% of patients with a known malignancy at autopsy. Common malignancies with pericardial involvement include breast and lung carcinomas, leukemia, melanoma, and lymphoma (2).

Clinical presentation

Chest pain is the primary presenting symptom of acute pericarditis. It is typically described as sharp, worsening with inspiration, and relieved on sitting upright and leaning forward (2). The pain is commonly felt over the anterior chest but can radiate to the trapezius ridge, shoulder, arm, or epigastrium. It is also associated with dyspnea. Other nonspecific symptoms include hiccups, fever, cough, hoarseness, palpitations, nausea, and vomiting (2).

A pericardial friction rub is the cardinal physical finding in acute pericarditis. Typically described as harsh, scratching, grating, and high-pitched, this sound is often heard best at end expiration when the patient is leaning forward. The pericardial friction rub can be transient and may vary in quality and intensity. It classically consists of three components associated with cardiac motion during ventricular systole, early diastolic filling, and atrial contraction. However, all three components often are not evident during clinical examination (1). In one series (1), all three components were present less than 50% of the time.

There are few additional specific physical findings in acute pericarditis. However, patients should be evaluated for signs of cardiac tamponade, including muffled heart sounds, tachycardia, hypotension, and elevated jugular venous pressure.

Evaluation

Initial evaluation of suspected acute pericarditis should include an ECG. When indicated, the workup also may include laboratory studies to measure markers of inflammation and myocardial injury, chest radiography, and echocardiography. Pericardiocentesis and pericardial biopsy are only rarely indicated.

Twelve-lead ECG
Abnormalities are seen on the ECG in up to 90% of cases of acute pericarditis (12). The pericardium is electrically inert; therefore, changes in the ECG are thought to be due to superficial myocardial inflammation (13). Four stages of electrocardiographic changes have been classically described (12) (table 2: not shown), although progression through all four stages occurs in less than 50% of patients. The most sensitive finding is diffuse ST-segment elevation. However, studies have shown that the initial change is PR-segment deviation (13) (figure 1).

Differential diagnosis in chest pain can be broad, and the ECG is often helpful in differentiating acute pericarditis from other causes. Some distinguishing features seen on the ECG in patients with pericarditis include concave ST segments, diffuse ST-segment elevation, and absence of reciprocal changes (12) (table 3: not shown).

Laboratory studies
Markers of acute inflammation, such as C-reactive protein, erythrocyte sedimentation rate, and leukocyte count, are commonly elevated (2). Markers of myocardial injury, such as creatine kinase-MB and cardiac troponin I, also may be elevated in patients with acute pericarditis (14). Although troponin levels are often used in the diagnosis of acute coronary syndromes, several reports have documented elevations of troponin I in up to 71% of patients with acute pericarditis (14,15). It is hypothesized that the mechanism involves inflammation of the subepicardial myocytes. In one study (14), the median peak cardiac troponin I concentration was 21.4 ng/mL, which is within the range commonly seen in acute coronary syndromes. In a study by Bonnefoy and colleagues (15), an increase in cardiac troponin I level was seen only in patients with ST-segment elevation and was more likely to occur in younger patients and those with a recent infection (15).

Chest radiography
Chest radiography usually has a limited role in the evaluation of acute pericarditis. In the presence of a large pericardial effusion (at least 250 mL), a radiograph may show an enlarged cardiac silhouette (2).

Echocardiography
Most authorities recommend obtaining an echocardiogram in patients in whom acute pericarditis is suspected. Although the echocardiogram does not help distinguish between causes of acute pericarditis, it is sensitive for detecting a pericardial effusion. When there is clinical suspicion of acute pericarditis, the presence of an effusion supports the diagnosis; however, this finding is not specific, because 8% to 15% of healthy, asymptomatic people have effusions (1).

Pericardiocentesis
The role of pericardiocentesis in the evaluation of acute pericarditis has been controversial. Many investigators have evaluated its role as both a diagnostic and a therapeutic procedure. In one prospective evaluation of patients with acute pericarditis (16), the yield of diagnostic pericardiocentesis (in the presence of persistent illness or suspicion of purulent pericarditis) was 6%, whereas the diagnostic yield of therapeutic pericardiocentesis (for treatment of tamponade) was 29%. In another study (17), investigators reviewed their 6-year experience with patients who had a large pericardial effusion without hemodynamic compromise. Pericardial drainage in these patients had a diagnostic yield of 7% and had a limited role in the evolution of the effusion. On the basis of these studies, routine diagnostic pericardiocentesis is not recommended, but the procedure is useful for treatment of cardiac tamponade and in cases of suspected purulent pericarditis.

Pericardial biopsy
Pericardial biopsy and pericardiectomy also have a low diagnostic yield. These procedures should be reserved for therapeutic indications or, rarely, for diagnosis in cases of prolonged illness when tuberculosis is highly suspected (16).

Complications

Idiopathic acute pericarditis is self-limited, and symptoms and laboratory abnormalities usually resolve within 2 to 6 weeks. However, several potential complications, including recurrent pericarditis, cardiac tamponade, and constrictive pericarditis, should be considered in patients who have a history of acute pericarditis.

The most common complication of acute pericarditis is recurrent pericardial inflammation, which develops in 15% to 32% of patients (18). Like acute pericarditis, this disease presents with severe chest pain and has many potential causes. Risk factors for recurrent pericarditis include chronic illness, such as cancer or connective tissue disease.

Pericardial effusions can develop in response to inflammation of the pericardium. Rapid or large accumulation of fluid in the pericardium can cause increased intrapericardial pressure, which may lead to cardiac tamponade. Symptoms of an effusion may include dyspnea, cough, dysphagia, and hoarseness, but none of these symptoms is a sensitive indicator of the presence of a pericardial effusion (2). Echocardiography is a sensitive and specific tool for identification and follow-up of significant effusions. Pericardial effusions associated with cardiac tamponade require prompt drainage.

Lastly, constrictive pericarditis occurs when the pericardium has become thickened, fibrotic, and calcified, resulting in impaired diastolic filling (1). Affected patients often present with symptoms and signs suggestive of congestive heart failure, such as dyspnea, peripheral edema, abdominal distention, elevated jugular venous pressure, and Kussmaul's sign. Patients in whom constrictive pericarditis is suspected should undergo echocardiography as well as right and left heart catheterization.

Treatment

Treatment of acute pericarditis should be directed toward the underlying cause, if identified. The other goals of therapy include pain relief and resolution of inflammation and effusion. Because most cases are idiopathic or viral, treatment is usually supportive. Bed rest can be helpful in severe cases, because activity can worsen symptoms. It is generally accepted that anticoagulation should be avoided, when possible, to minimize the risk of hemopericardium. Initial hospitalization should be considered for patients in whom myocardial infarction, tamponade, and purulent disease are a concern. Antimicrobial therapy is reserved for patients with documented purulent or tuberculous pericarditis (1).

The mainstay of therapy is nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin, indomethacin (Indocin), naproxen (eg, Napro-syn), and ketorolac tromethamine (Toradol) can be helpful in symptomatic improvement (2). These medications also may prevent further inflammation. Corticosteroids should be reserved for patients whose symptoms are refractory to NSAID therapy (2).

Most cases of recurrent pericarditis are idiopathic, although the disease has been presumed to have an immunologic basis. NSAIDs remain the cornerstone of therapy. Colchicine, an anti-inflammatory drug used most commonly in acute arthritis, has also shown promise in the treatment of recurrent pericarditis (18). In recalcitrant cases, immunosuppressive therapy with high-dose corticosteroids, cyclophosphamide (Cytoxan, Neosar), or azathioprine (Imuran) has been used with variable success, although the data are limited (19).

Summary

Acute pericarditis is a common disease that typically is diagnosed on the basis of its classic chest pain, pericardial friction rub, and changes on ECG. Although most cases are idiopathic and self-limited, numerous causes should be considered. The diagnostic yield of extensive laboratory evaluation and pericardiocentesis is very low, and invasive procedures should be limited to patients in whom therapeutic intervention is necessary. Treatment should focus on symptomatic relief, usually through use of NSAIDs, and patients should be carefully evaluated and monitored for common complications of the disease.

References

1. Lorell BH. Pericardial diseases. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia: WB Saunders, 1997:1478-85
2. Aikat S, Ghaffari S. A review of pericardial diseases: clinical, ECG and hemodynamic features and management. Cleve Clin J Med 2000;67(12):903-14
3. Farraj RS, McCully RB, Oh JK, et al. Mycoplasma-associated pericarditis. Mayo Clin Proc 1997;72(1):33-6
4. Brook I. Pericarditis due to anaerobic bacteria. Cardiology 2002;97(2):55-8
5. Paz A, Potasman I. Mycoplasma-associated carditis: case reports and review. Cardiology 2002;97(2):83-8
6. de Meester A, Luwaert R, Chaudron JM. Symptomatic pericarditis after influenza vaccination: report of two cases. Chest 2000;117(6):1803-5
7. Gunukula SR, Spodick DH. Pericardial disease in renal patients. Semin Nephrol 2001;21(1):52-6
8. Zayas R, Anguita M, Torres F, et al. Incidence of specific etiology and role of methods for specific etiologic diagnosis of primary acute pericarditis. Am J Cardiol 1995;75(5):378-82
9. Savoia MC, Oxman MN. Myocarditis and pericarditis. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingstone, 2000:925-41
10. Klacsmann PG, Bulkley BH, Hutchins GM. The changed spectrum of purulent pericarditis: an 86-year autopsy experience in 200 patients. Am J Med 1977;63(5):666-73
11. Sagrista-Sauleda J, Permanyer-Miralda G, Soler-Soler J. Tuberculous pericarditis: ten-year experience with a prospective protocol for diagnosis and treatment. J Am Coll Cardiol 1988;1(4):724-8
12. Marinella MA. Electrocardiographic manifestations and differential diagnosis of acute pericarditis. Am Fam Physician 1998;57(4):699-704
13. Baljepally R, Spodick DH. PR-segment deviation as the initial electrocardiographic response in acute pericarditis. Am J Cardiol 1998;81(12):1505-6
14. Brandt RR, Filzmaier K, Hanrath P. Circulating cardiac troponin I in acute pericarditis. Am J Cardiol 2001;87(11):1326-8
15. Bonnefoy E, Godon P, Kirkorian G, et al. Serum cardiac troponin I and ST-segment elevation in patients with acute pericarditis. Eur Heart J 2000;21(10):832-6
16. Permanyer-Miralda G, Sagrista-Sauleda J, Soler-Soler J. Primary acute pericardial disease: a prospective series of 231 consecutive patients. Am J Cardiol 1985;56(10):623-30
17. Merce J, Sagrista-Sauleda J, Permanyer-Miralda G, et al. Should pericardial drainage be performed routinely in patients who have a large pericardial effusion without tamponade? Am J Med 1998;105(2):106-9
18. Adler Y, Finkelstein Y, Guindo J, et al. Colchicine treatment for recurrent pericarditis: a decade of experience. Circulation 1998;97(21):2183-5
19. Marcolongo R, Russo R, Laveder F, et al. Immunosuppressive therapy prevents recurrent pericarditis. J Am Coll Cardiol 1995;26(5):1276-9

Dr Ross is a fellow, division of cardiology, Oregon Health & Science University School of Medicine, Portland. Dr Grauer is assistant professor of medicine, Oregon Health & Science University School of Medicine, and staff cardiologist, Portland Veterans Affairs Medical Center. Correspondence: Susan E. Grauer, MD, Cardiology Section (P-3-CARD), Portland Veterans Affairs Medical Center, PO Box 1034, Portland, OR 97207. E-mail: grauers@ohsu.edu.

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