Diagnosing KRISHAN K. GOYLE, M.D., and ANNE D. WALLING, M.D. University of Kansas School of Medicine, Wichita, Kansas

Pericarditis, or of the , is most often caused by viral . It can also develop as a result of bacterial or other infection, autoimmune , renal failure, to the mediastinal area, and the effects of certain drugs (notably hydrala- zine and procainamide). The clinical features of pericarditis depend on its cause, as well as the volume and type of effusion. Patients with uncomplicated pericarditis have pleu- ritic-type chest that radiates to the left shoulder and may be relieved by leaning forward. Chest radiographs, Doppler studies, and laboratory tests confirm the diagno- sis and provide information about the degree of effusion. In most patients, pericarditis is mild and resolves spontaneously, although treatment with a nonsteroidal anti-inflam- matory drug or a short course of a may be helpful. When a large peri- cardial effusion is produced, cardiac function may be compromised, and cardiac tam- ponade can occur. In patients with longstanding inflammation, the pericardium becomes fibrous or calcified, resulting in constriction of the . Drainage or surgical intervention may be necessary in patients with complicated pericarditis. (Am Fam Physi- cian 2002;66:1695-702. Copyright© 2002 American Academy of Family Physicians.)

ericarditis is inflammation of the physicians should be alert to the possibility of pericardial sac surrounding the pericarditis in patients with , heart and the origins of the great because misdiagnosis can have potentially vessels.1 The condition is most fatal consequences. In particular, hemorrhage often caused by a viral infection and fatal cardiac compression can occur if Pand generally resolves in a few weeks with no thrombolytic therapy is given to patients who sequelae. have pericarditis. Severe pericardial syndromes are relatively uncommon, and their clinical features are Etiology largely determined by the amount and type of Although viral infection is the most com- fluid produced by the inflammatory process.1,2 mon cause of pericarditis,5 the condition has The normal pericardial sac contains 15 to many possible causes6,7 (Table 1),including 20 mL (maximum: 50 mL) of serous fluid, bacterial infection, myocardial , which lubricates cardiac motion.3 In pericardi- trauma, malignancy, , hypothyroidism, tis, the accumulation of serous fluid, inflam- vascular disease, and the effects of matory cells, and fibrin may compromise car- certain drugs, notably (Apreso- diac function. line) and procainamide (Pronestyl). Purulent Over time, pericarditis can result in chronic pericarditis as a result of bacterial infection inflammation with thickening and, ultimately, (e.g., ) is now rare, but human calcification of the pericardium. This condi- infection has tion is known as “chronic constrictive peri- become an increasingly common cause of the .” Conversely, rapid accumulation of condition.8,9 Many that cause peri- serous fluid can result in compression of carditis, particularly fungal and nonbacterial the cardiac chambers, with dire hemodynamic infections, occur most often in immuno- consequences.3,4 This condition, which is compromised patients. called “,”may occur in up to Pericarditis may complicate myocardial 15 percent of patients with severe pericarditis.2 infarction on the second to fourth day after the Pericarditis can mimic other conditions, acute event as a reaction to underlying necrotic especially . Family myocardium. The condition may also be a

NOVEMBER 1, 2002 / VOLUME 66, NUMBER 9 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1695 TABLE 1 Etiology of Pericarditis prominent feature of postmyocardial infarc- Idiopathic (nonspecific, probably viral) tion syndrome (Dressler’s syndrome), which Infectious causes develops weeks to months after acute infarc- : A and B, hepatitis viruses, human immunodeficiency virus, measles virus, virus, varicella virus tion. In this situation, pericarditis occurs : gram-positive and gram-negative organisms; rarely, Mycobacterium because of a late autoimmune reaction stimu- species (tuberculosis) lated by the entry of necrotic myocardial tissue Fungi (most often in immunocompromised patients): Blastomyces dermatitidis, into the circulation, where it acts as an antigen. species, Histoplasma capsulatum Pericarditis is a feature of several autoim- Noninfectious causes mune conditions, especially systemic Acute myocardial infarction* erythematosus. It is also associated with renal Renal failure† failure and hemodialysis. Furthermore, peri- Malignancy: breast , cancer, Hodgkin’s disease, leukemia, lymphoma by local invasion carditis can develop because of injury to the Radiation therapy (usually for breast or lung cancer) pericardium as a result of trauma, surgery, Autoimmune disorders: mixed connective tissue disorder, hypothyroidism, instrumentation, or radiation therapy. inflammatory bowel disease, , systemic lupus erythematosus, Wegener’s granulomatosis, Takayasu’s arteritis6 Pathophysiology and Classification Trauma (including surgery): closed procedures and pacemaker implantation Depending on the underlying cause, the (puncture of myocardium) acute inflammatory response in pericarditis Drugs‡: hydralazine (Apresoline), procainamide (Pronestyl), phenytoin (Dilantin), (e.g., Nydrazid); with rifampin (Rifamate), may produce serous fluid, , or dense fibrin- phenylbutazone, dantrolene (Dantrium), doxorubicin (Adriamycin, Rubex), ous material. Viral pericarditis usually results methysergide (Sansert), , mesalamine (Rowasa)7 in small accumulations of serous fluid that resolve spontaneously or require minimal *— may occur on the second to fourth day after acute therapeutic intervention. Even large volumes myocardial infarction as a reaction to underlying necrotic myocardium in up to of serous fluid (up to 250 mL) may not cause 25 percent of patients. It can also develop weeks to months after myocardial significant clinical signs or symptoms if accu- infarction in patients with postmyocardial infarction syndrome (Dressler’s syn- drome); in this situation, pericarditis occurs because of a late autoimmune reac- mulation is gradual. The effusion may only be tion stimulated by the entry of necrotic myocardial tissue into the circulation, apparent as an enlarged cardiac silhouette on where it acts as an antigen. the .3 †—Pericarditis in uremia indicates a need for ; pericarditis may also be Conversely, large acute accumulations of associated with hemodialysis. pericardial fluid may cause intrapericardial ‡—Listed in relative order of frequency. pressure to rise, thereby impeding filling of the right side of the heart through the superior vena cava and inferior vena cava. Acutely, this situation can result in cardiac tamponade. If The Authors the pericarditis process continues and the fluid KRISHAN K. GOYLE, M.D., has a private practice and is also associate pro- organizes into a thickened (even calcified) fessor at the University of Kansas School of Medicine, Wichita. Dr. Goyle received his coating, the resultant constrictive pericarditis medical degree from All Institute of Medical Sciences, New Delhi. He completed may mimic restrictive .4,10,11 an internal medicine residency at the University of Rochester (N.Y.) and a cardiology fellowship at the Cleveland Clinic Foundation. Thus, pericarditis may be classified as acute, subacute, or chronic, depending on the under- ANNE D. WALLING, M.D., is associate dean for faculty development and professor in the Department of Family and Community Medicine at the University of Kansas School of lying pathophysiologic process (Table 2). Medicine, Wichita. Dr. Walling received her medical degree from the University of St. Andrews, Scotland, and completed postdoctoral training in community medicine and Hemodynamic Considerations in London. She is a former secretary-treasurer of the Society of Teachers of Family Medicine and presently serves as associate editor of American Family Physician. Changes in the jugular veins and the rela- tionship of those changes to respiration can be Address correspondence to Krishan K. Goyle, M.D., University of Kansas School of Medicine, 1010 N. Kansas, Suite 3207, Wichita, KS 67214-3199 (e-mail: kgoyle@ extremely useful in differentiating pericarditis yahoo.com). Reprints are not available from the authors. from other causes of chest pain and related

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in early right ventricular diastolic collapse and TABLE 2 late diastolic right atrial collapse, because pres- Classification of Pericarditis sures are lowest in diastole. The y descent is blunted because the right cannot (<6 weeks) expand, but the x descent remains normal. In Effusive cardiac tamponade, some blood (though less Fibrinous than normal) still flows toward the right side of Subacute pericarditis (>6 weeks to 6 months) the heart during inspiration. Because the car- Chronic pericarditis (>6 months) diac chambers are inhibited from dilating, the Effusive inflow causes the intraventricular septum to Adhesive Effusive-adhesive shift to the left, which further decreases left Constrictive ventricular capacity. The hemodynamic changes can cause sys- tolic to fall by 10 mm Hg or more during inspiration. This situation, symptoms. These changes also can be crucial termed “,” is the classic hall- in recognizing cardiac tamponade and con- mark of cardiac tamponade. Pulsus paradoxus strictive pericarditis.1-3,11 is detectable in 70 to 80 percent of patients The normal jugular vein examination shows with cardiac tamponade and in about one two positive waves (the a wave during atrial third of patients with pericarditis.2 and the v wave during ventricular sys- In constrictive pericarditis, no forward flow tole) and two negative waves (the x descent occurs from the superior vena cava and the during atrial diastole and the y descent during inferior vena cava during inspiration. This ventricular systole). During inspiration, lung results in Kussmaul’s sign, which is a para- expansion causes negative intrathoracic pres- doxic inspiratory swelling of the neck veins. sure that is transmitted to the pericardium and Because blood flow to the right side of the cardiac chambers, leading to dilation of the heart does not increase, no septal shift occurs, chambers. As a result, the right chambers of and pulsus paradoxus is not common in con- the heart fill with blood from the superior vena strictive pericarditis. cava and the inferior vena cava, and the left chambers fill because of forward flow in the Clinical Features pulmonary veins. Patients usually recall a nonspecific pro- Even with a moderately large effusion, mild drome of , , and chest pain, espe- acute pericarditis usually has no hemody- cially in viral or idiopathic pericarditis. The namic impact on the heart. Hence, jugular chest pain is typically pleuritic and radiates to venous profiles are generally normal. the left shoulder and, characteristically, the left Conversely, cardiac tamponade and con- trapezius musculature. The pain is exacer- strictive pericarditis lead to important and dis- bated by inspiration or recumbency and tinctive hemodynamic changes. Because the relieved to some extent by leaning forward. heart is constricted by fluid or a rigid fibrinous Patients may have additional symptoms, or calcified pericardium, negative intratho- depending on the etiology of the pericarditis racic pressure during inspiration is not trans- and the presence of complications. mitted to the pericardial sac. Consequently, Clinical signs may be subtle. A pericardial intrapericardial and intracardiac pressures friction rub may or may not be present. Large remain elevated, and intrapericardial pressure effusions are unlikely to produce a pericardial equals or exceeds right atrial pressure. rub. With large, slowly accumulating effu- In cardiac tamponade, this situation results sions, there may be dullness to percussion in

NOVEMBER 1, 2002 / VOLUME 66, NUMBER 9 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1697 the scapular region because of compression of the left lung (Ewart’s sign). As previously noted, acute, rapid accumula- tion of fluid in the pericardium causes signs of acute hemodynamic compromise in cardiac tamponade. Patients with this condition develop , , pulsus para- doxus, and distended neck veins. Although these patients appear to be in acute distress (similar to cardiac failure and ), their are clear on . In chronic constrictive pericarditis,4 the neck veins are markedly distended, but patients do not appear distressed and show no evidence of pulsus paradoxus. During inspiration, the neck veins become distended (normally, they collapse). The jugular venous pulse shows a sharp y descent because of rapid right ventricular filling in early diastole. A sharp heart sound called a “pericardial knock” is heard in early diastole. Unless other problems are present, the lungs are usually clear on auscultation. Because of congestion of the inferior vena cava, the liver is enlarged, and ascites and peripheral leg edema are evi- dent. Clinical features may mimic those of restrictive cardiomyopathy.

Diagnosis The diagnosis of pericarditis and its compli- cations requires a high index of suspicion. Clinical features and the probability of a cause of pericarditis (Table 1) may assist in recogni- The rightsholder did not tion. Potential confirmatory studies include the electrocardiogram (ECG), the chest radio- grant rights to reproduce graph, Doppler studies, and selected labora- this item in electronic tory tests. A suggested approach to the diag- media. For the missing nosis of pericarditis is provided in Figure 1.2 item, see the original print version of this publication. In acute pericarditis, the ECG typically shows ST-segment elevation in all leads, with an upward concavity of the elevation (so- FIGURE 1. called “smiling face”). The PR segment is depressed. Unlike myocardial infarction, there is no reciprocal change, and T waves are not inverted.12-15 Pericarditis

In this situation, the includes acute myocardial infarction and nor- When pericarditis is suspected, an electrocardiogram mal-variant repolarization abnormality. It is and a chest radiograph should be obtained. Laboratory particularly important to distinguish peri- tests frequently include a complete blood count, an carditis from acute myocardial infarction, erythrocyte sedimentation rate, cardiac enzyme levels, and because thrombolytic therapy could have dis- astrous effects in patients with pericarditis. serum chemistries. Characteristic features of acute pericarditis, acute myocardial infarction, and early repo- larization are summarized in Table 3.Exam- ples illustrating the ECG differentiation of the cardiography. This imaging modality can three conditions are provided in Figure 2.16 demonstrate moderate or large effusions. In In cardiac tamponade, the ECG shows elec- cardiac tamponade, Doppler examination may trical alternans as the heart “floats” in relation show the characteristic swinging motion of the to the recording leads. Chronic constrictive heart that gives rise to . pericarditis presents with low voltage of the Doppler examination can also show the QRS complex and diffuse flattening or inver- reversal of inflow velocities in the tricuspid sion of the T waves. Atrial occurs in and mitral valves during inspiration and expi- one third of patients with pericardial disease. ration. Divergence of right and left ventricular systolic pressures is demonstrated in cardiac CHEST RADIOGRAPHY tamponade and constrictive pericarditis. If more than 250 mL of fluid has accumu- Doppler studies differentiate pericarditis from lated, the cardiac silhouette is usually enlarged restrictive cardiomyopathy.3,10,17 on the chest radiograph. Smaller accumulations may appear normal. In constrictive pericarditis, LABORATORY TESTS calcification may be seen around the heart. Laboratory studies are useful for excluding other possible causes of symptoms and clari- DOPPLER STUDIES fying the underlying cause of pericarditis. The diagnostic test of choice for large effu- Testing is individualized but frequently in- sions, cardiac tamponade, and constrictive cludes a complete count (CBC), an pericarditis is two-dimensional Doppler echo- erythrocyte sedimentation rate (ESR), cardiac

TABLE 3 Electrocardiographic Differentiation of Pericarditis

Acute pericarditis Acute myocardial infarction Early repolarization ST-segment elevation in ST-segment elevation in anatomically ST-segment elevation in middle and many leads, with no contiguous leads, with possible left precordial leads, but may be ST-segment depression reciprocal ST-segment depression widespread Upward concave ST-segment Upward convex ST-segment elevation Upward convex ST-segment elevation elevation No T-wave inversion in leads T-wave inversion in leads with May have T-wave inversion in leads with ST-segment elevation ST-segment elevation as myocardial with ST-segment elevation infarction evolves PR-segment depression No PR-segment depression No PR-segment depression Q waves during evolution May have Q waves during evolution No Q waves

NOVEMBER 1, 2002 / VOLUME 66, NUMBER 9 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1699 A. Acute pericarditis. The ST segment (long arrows) is elevated in all leads (universal elevation in contrast to the focal elevation in acute myocardial infarction), with no reciprocal change. The ST-segment elevation shows upward concavity (so-called “smiling face”). The PR interval (short arrow) is depressed because of inflammatory changes involving the atrial wall.

I aVR V1 V4

V2 II aVL V5

III aVF V3 V6

B. Acute myocardial infarction. The ST segment (long arrow) is elevated in leads II, III, and aVF, and depressed (short arrow) in leads I,

aVL, and V1, V2, and V3 (focal elevation in segment of injury, with reciprocal ST-segment depression). The ST elevation is convex upward (tomb shape or so-called “sad face”). Figure continues

FIGURE 2. Electrocardiographic differentiation of pericarditis from acute myocardial infarction and early repolarization. Information from reference 16.

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FIGURE 2 continued

C. Early repolarization. ST-segment elevation (long arrow) is present in all leads, with no reciprocal depression. Peaked T waves (short arrow) are seen in the middle precordial leads. No Q waves are present.

enzyme levels, and serum chemistries. Non- enzyme levels. Patients also should be hospi- specific elevations in the CBC and ESR are talized if they have pulsus paradoxus, electri- common in patients with pericarditis. cal alternans on the ECG, or a large pericardial effusion. Patients with chronic, large pericar- Treatment dial effusion may be asymptomatic but can Most patients with idiopathic pericarditis develop cardiac tamponade precipitously. can be managed conservatively with a non- Thus, is indicated, and steroidal anti-inflammatory drug (NSAID) pericardectomy should be performed if the such as indomethacin (Indocin), effusion recurs after percutaneous drainage.11 (e.g., Advil, Motrin), or acetylsalicylic acid Pericardiocentesis is best performed in a (). These agents are believed to be controlled setting by an experienced physi- equally effective, and the literature does not cian. The patient is placed in a semirecumbent indicate an NSAID of choice for pericarditis. position (approximately 45- to 60-degree ele- Patients who do not respond to an NSAID vation). The pericardiocentesis needle is may need a short course of a corticosteroid, introduced into the subxiphoid angle and usually in a dosage of 5 to 10 mg aimed toward the left shoulder. Distally, the per day for one to two weeks. Rarely, patients needle is attached to an ECG monitor. Detec- do not respond to this therapy or show evi- tion of ST-segment elevation during the pro- dence of recurrent pericarditis. These patients cedure suggests injury to the myocardium. In require a prolonged corticosteroid course (i.e., cardiac tamponade, emergency pericardio- several months). centesis can be lifesaving, because drainage of may be a useful alternative in patients who cannot take NSAIDs and corti- costeroids or have major side effects with Idiopathic pericarditis can usually be managed conservatively 18 these agents. with a nonsteroidal anti-inflammatory drug or a short course Indications for hospitalization include ele- of a corticosteroid. vated neck veins, tachycardia, hypotension, poor pain control, and elevated cardiac

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3. Murphy JG. Mayo Clinic cardiology review. 2d ed. Philadelphia: Lippincott Williams & Wilkins, 2000: Emergency pericardiocentesis can be lifesaving in patients 509-32. with cardiac tamponade. A pericardial window may be 4. Myers RB, Spodick DH. Constrictive pericarditis: clinical and pathophysiologic characteristics. Am needed in patients with uremic, malignant, or bacterial peri- Heart J 1999;138(2 pt 1):219-32. cardial effusion. 5. Goland S, Caspi A, Malnick SD. Idiopathic chronic pericardial effusion [Letter]. N Engl J Med 2000; 342:1449. 6. Narita H, Ohte N, Yoneyama A, Hashimoto T, Akita S, Sakuma N. Takayasu’s arteritis accompanied with even a small amount of fluid changes the vol- massive pericardial effusion—a case report. Angiol- ume-pressure relationship significantly. ogy 1999;50:421-5. 7. Sentongo TA, Piccoli DA. Recurrent pericarditis due For continuous drainage, a catheter may be to mesalamine hypersensitivity: a pediatric case left in the pericardial sac, or a pericardial win- report and review of the literature. J Pediatr Gas- dow may be created surgically. Pericardiocen- troenterol Nutr 1998;27:344-7. 8. Chen Y, Brennessel D, Walters J, Johnson M, Ros- tesis may result in recurrent effusive-adhesive ner F, Raza M. Human immunodeficiency virus– pericarditis, especially in uremic, malignant, associated pericardial effusion: report of 40 cases or bacterial pericardial effusions. These condi- and review of the literature. Am Heart J 1999;137: 516-21. tions frequently require the creation of a peri- 9. Silva-Cardoso J, Moura B, Martins L, Mota-Miranda cardial window. A, Rocha-Goncalves F, Lecour H. Pericardial involve- is the treatment of choice ment in human immunodeficiency virus infection. Chest 1999;115:418-22. for chronic constrictive pericarditis. In 10. Oh JK, Hatle LK, Seward JB, Danielson GK, Schaff asymptomatic patients and patients who are HV, Reeder GS, et al. Diagnostic role of Doppler not considered surgical candidates, cautious in constrictive pericarditis. J Am Coll Cardiol 1994;23:154-62. diuretic therapy may be considered. Because 11. Sagrista-Sauleda J, Angel J, Permanyer-Miralda G, atrial dysrhythmias (particularly atrial fibrilla- Soler-Soler J. Long-term follow-up of idiopathic tion) are common in patients with pericardi- chronic pericardial effusion. N Engl J Med 1999; 341:2054-9. tis, ventricular rate control should be initiated 12. Chan TC, Brady WJ, Pollack M. Electrocardio- using a calcium channel blocker (verapamil graphic manifestations: acute . [Calan, Isoptin] or diltiazem [Cardizem], but J Emerg Med 1999;17: 865-72. 13. Jain A. “Tombstone” anterior ST-segment eleva- not [Procardia]) or a . tions secondary to acute pericarditis: the role of In certain situations, patients with cardiac two-dimensional echocardiogram. Clin Cardiol tamponade or must go 1997;20:404-6. 14. Marinella MA. Electrocardiographic manifestations directly to surgery. Needle pericardiocentesis and differential diagnosis of acute pericarditis. Am will exsanguinate patients with proximal aor- Fam Physician 1998;57:699-704. tic dissection or cardiac rupture.3 15. Baljepally R, Spodick DH. PR-segment deviation as the initial electrocardiographic response in acute The authors indicate that they do not have any con- pericarditis. Am J Cardiol 1998;81:1505-6. flicts of interest. Sources of funding: none reported. 16. Debehnke DJ. Cardiac-related acute infectious dis- ease. In: Gibler WB, Aufderheide TP, eds. Emer- REFERENCES gency cardiac care. St. Louis: Mosby, 1994:463- 88. 1. Braunwald E. Heart disease: a textbook of cardio- 17. Eisenberg MJ, Oken K, Guerrero S, Saniei MA, vascular medicine. 5th ed. Philadelphia: Saunders, Schiller NB. Prognostic value of echocardiography 1997:1478-523. in hospitalized patients with pericardial effusion. 2. MKSAP 12: medical knowledge self-assessment Am J Cardiol 1992;70:934-9. program. Philadelphia: American College of Physi- 18. Adler Y, Guindo J, Finkelstein Y, Khouri A, Assali A, cians–American Society of Internal Medicine, Bayes-Genis A, et al. Colchicine for large pericar- 2001:50-4. dial effusion. Clin Cardiol 1998;21:143-4.

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