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Pericarditis: Putting the
Pieces Together
The disease has many possible causes and can take various forms. The author reviews these and other key factors to consider in diagnosing pericarditis.
By Jorge A. Martinez, MD, JD
Pericarditis is defined as inflammation of the pericardial sac surrounding the heart and origins of the great vessels. Idiopathic pericarditis is the most common form of the disease, but there are many other possible causes (see table below). In this article, I will review the various forms of pericarditis and their clinical presentation. Diagnostic testing and management strategies will also be discussed.
ANATOMY AND UNDERLYING CAUSES
The pericardium consists of a fibrous outer parietal layer and a thin inner visceral layer. The fibrous pericardium surrounds the heart and attaches to the diaphragm, sternum, and mediastinum, while the visceral layer lies adjacent to the surface of the heart. The space between the fibrous and visceral pericardium contains approximately 15 to 60 ml of serous fluid that allows the heart to move freely within the pericardial sac. The electrolyte and protein composition of the pericardial fluid is similar to that of plasma. The pericardium’s primary function is to protect the heart from direct injury and to inhibit the spread of infection or inflammation from adjacent structures.
Idiopathic pericarditis, the most common form, is usually viral in origin. Viruses that can cause pericarditis include coxsackie, varicella, HIV, adenovirus, echovirus, and hepatitis virus. Infectious or purulent pericarditis is caused by pathogenic organisms, including bacteria, Mycobacterium tuberculosis, mycoplasma, parasites, and fungi.
Other causes of pericarditis include malignancies; connective tissue diseases, including systemic lupus erythematosus and rheumatoid arthritis; metabolic disorders, such as uremia and myxedema; radiation; trauma; and medications, specifically hydralazine, procainamide, dantrolene, and methysergide. Pericarditis may also develop as a complication of acute myocardial infarction (AMI).
CHEST PAIN AND FRICTION RUB
The clinical presentation of pericarditis includes chest pain, dyspnea, dysphagia, cough, and fever. Rarely, the disease may be subclinical and asymptomatic. This is especially true in post-AMI and purulent pericarditis. Furthermore, in the purulent form of the disease, systemic signs and symptoms related to the infective organism may overshadow the focal signs and symptoms of pericarditis.
Pericarditis is usually diagnosed by a history of chest pain in association with characteristic ECG changes. The chest pain is typically substernal and radiates to the neck, the left trapezius area, scapula, or shoulder. It may be sharp or dull and varies from mild to severe in intensity. In most cases, it is aggravated by motion, cough, and respiration. The pain is usually most severe when the patient is supine and is relieved by sitting up and leaning forward.
The most striking physical finding in pericarditis is a pericardial friction rub, which is found in approximately 85% of cases. The typical friction rub consists of three components during the cardiac cycle: systolic (ventricular systole), diastolic (early diastole), and presystolic (atrial contraction). The systolic component is heard most often. The rub is best appreciated with the patient sitting down and leaning forward or in the hands-and-knees position (where the patient kneels with the palms of his hands at the same level as his knees).
Usually described as a scratchy, Velcro-like, or leather-like sound, the rub is best heard with the diaphragm of the stethoscope along the left lower sternal border or at the apex. It may be transient or it may wax and wane, and its intensity may vary with changes in position.
PERICARDIAL EFFUSION: COMMON FINDING
An increase in the fluid volume within the pericardial sac is known as pericardial effusion, a common finding in pericarditis. Physical findings of pericardial effusion include muffled heart sounds, an increased area of cardiac dullness on percussion, and Ewart’s sign (dullness and bronchial breathing between the tip of the left scapula and the vertebral column). Ewart’s sign signifies atelectasis of the left lower lobe of the lung due to compression of the lobe by the expanded pericardial sac. It is more common with large pericardial effusions.
The amount of fluid in the pericardial sac, as well as the rapidity of fluid accumulation, can affect the hemodynamic function of the heart. Up to two liters of fluid can accumulate gradually in the pericardial sac without significantly increasing intrapericardial pressure. On the other hand, a rapid buildup of fluid within the pericardial sac results in a sudden and dramatic increase in pressure. The elevated pressure, in turn, compresses the right atrium and ventricle, impeding venous return to the heart. Encumbered atrial and ventricular filling results in reduced stroke volume and cardiac output.
The end result is a fall in cardiac output, systemic hypotension, and shock—the clinical condition called pericardial tamponade. Clinical findings in pericardial tamponade include hypotension, tachycardia, anxiety, distended jugular veins, muffled heart sounds, change in mental status, and pulsus paradoxus. Elevated right atrial venous pressure causes the jugular vein distension. Pulsus paradoxus is present when systolic blood pressure falls by more than 10 mm Hg during inspiration. In severe cases, blood pressure may disappear completely with inspiration. Importantly, pulsus paradoxus is not specific for pericardial tamponade. It may also be seen in chronic obstructive pulmonary disease, bronchial asthma, pulmonary embolism, right ventricular infarction, and shock.
Pericardial tamponade is treated with immediate pericardiocentesis at the bedside. It should be performed with cardiac monitoring and imaging studies, such as echocardiography, computed tomography (CT), or cardiac fluoroscopy.
INFARCTION PERICARDITIS AND DRESSLER’S SYNDROME
Two different types of pericarditis may develop subsequent to AMI: infarction pericarditis and postcardiac injury syndrome (better known as Dressler’s syndrome). Infarction pericarditis is the result of the inflammatory process that occurs subsequent to transmural myocardial necrosis. This condition usually occurs within the first three days post-AMI and resolves within seven days. Chest pain in infarction pericarditis is often pleuritic in nature and radiates to the trapezius regions. While it is an important clinical manifestation of infarction pericarditis, chest pain is not always present. Instead, a pericardial friction rub, which is the result of the deposition of fibrinous exudate during the inflammatory process, is a more common finding. Thus, daily cardiac auscultation is important in diagnosing infarction pericarditis. If a friction rub is heard, an echocardiogram should be performed to search for concurrent pericardial effusion.
Importantly, the diagnosis of infarction pericarditis is one of exclusion. Other causes of post-AMI chest pain, including reinfarction, infarct extension, pulmonary embolus, pneumonia, free wall rupture, and acute ventricular septal defect, need to be ruled out. Accordingly, an emergent chest x-ray, ECG, cardiac enzymes, and echocardiogram should be performed. Physical examination should include auscultation for new gallops, murmurs, and a pericardial friction rub.
Infarction pericarditis is associated with larger, anterior infarctions and increased morbidity and mortality. The incidence of this condition has diminished, however, most likely because reperfusion therapy has decreased the incidence of transmural myocardial necrosis.
The second type of pericarditis in the post-AMI period is Dressler’s syndrome. This is a late complication that occurs weeks to months after an AMI; it is a rare occurrence in the first week post-AMI. The predominant findings are fatigue; pleuritic chest pain; pericardial friction rub; fever up to 104ºF; leukocytosis; elevated erythrocyte sedimentation rate (ESR); pleural and pericardial effusions; and pulmonary infiltrates.
Dressler’s syndrome is thought to be due to an abnormal immune response to necrotic cardiac tissue. It is postulated that myocardial injury causes the release of myocardial antigens, which stimulates the formation of antibodies to myocardial tissue. This results in the formation of immune complexes, which are deposited into the pericardium, lungs, and pleura with a resultant inflammatory reaction in these tissues. Like infarction pericarditis, postcardiac injury syndrome has virtually disappeared since the advent of reperfusion therapies.
PURULENT PERICARDITIS
Purulent or infectious pericarditis is less common than in the pre-antibiotic era. Before the routine use of antibiotics, the most common cause of purulent pericarditis was gram-positive bacteria, primarily Streptococcus pneumoniae. As a result of worldwide antibiotic use, the most common causative agents now are gram-negative bacteria, atypical bacteria, and fungi. The table below lists the various causes of purulent pericarditis.
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Purulent pericarditis occurs most commonly in children and immunocompromised individuals. It usually results from the direct extension of a pulmonary or mediastinal infection to the pericardium or from the hematogenous seeding of the pericardium during bacteremia. The most common infectious processes underlying purulent pericarditis are pneumonia and empyema. It has also been linked to thoracic surgery, bacterial endocarditis, and hemodialysis. If it is untreated, the mortality rate is nearly 100%, but even with prompt treatment with intravenous antibiotics and pericardial drainage, the mortality rate is still close to 40%.
The onset of purulent pericarditis may be acute, with rapid progression to pericardial tamponade, or it may be insidious. Thus, a high index of suspicion is necessary to make the diagnosis. Clinical findings include fever, chills, dyspnea, tachypnea, cough, weakness, and tachycardia out of proportion to the fever. Systemic signs and symptoms of the causative organism may predominate over the localized signs and symptoms of pericarditis. Classic symptoms of pericarditis, such as chest pain and a pericardial friction rub, occur in only about 50% of patients.
Common laboratory tests in suspected purulent pericarditis include a complete blood count with differential, ESR, protein purified derivative (PPD) skin test, bacterial and fungal blood cultures, viral titers and HIV blood tests, chest x-ray, and echocardiography. The goal is to detect the existence and extent of purulent pericarditis and to identify the causative infectious agent. In purulent pericarditis the white blood cell (WBC) count is markedly elevated with increased immature polymorphonuclear cells. The ESR is also significantly elevated. Chest x-rays may demonstrate cardiomegaly due to the purulent pericardial effusion. It may also reveal the causative process—for example, pneumonia or empyema. An echocardiogram will show the presence of a purulent pericardial effusion.
All patients with suspected purulent pericarditis should be started immediately on empiric intravenous antibiotics, including vancomycin, a third-generation cephalosporin, and an aminoglycoside. Emergent pericardiocentesis should be performed to acquire purulent pericardial fluid for culture and sensitivities and to address clinical pericardial tamponade. Complete drainage of the pericardium is essential. If the purulent effusion cannot be drained by pericardiocentesis, if it reaccumulates, or if it is too thick to aspirate, surgical pericardiotomy or pericardial window is necessary.
All patients with purulent pericarditis must be admitted to an intensive care unit, where modification of the antibiotic regimen and invasive intervention can be guided by pericardial aspirate cultures and sensitivities, echocardiography findings, and clinical response.
TB AND HIV PERICARDITIS
Mycobacterium tuberculosis (TB) is a common cause of purulent pericarditis worldwide and a major cause of pericarditis in immunocompromised individuals. It results from the retrograde spread of myobacteria from peribronchial, peritracheal, or mediastinal lymph nodes; from miliary TB; or from seeding from the lungs, spine, or sternum. Less than half of patients with TB pericarditis have pulmonary TB.
Typical findings include chest pain, fever, night sweats, weight loss, anorexia, weakness, and tachycardia. Pericardial effusion is found in about 50% of cases. The PPD skin test is negative in approximately one third of cases. Pericardial fluid should be aspirated to obtain fluid for culture and appropriate stains. However, cultures are only positive in about 50% of cases and acid-fast bacilli are rarely seen on microscopy. Cultures of pericardial tissue biopsy may enhance the diagnostic yield. Thus, pericardial fluid and tissue cultures are essential to make the diagnosis, establish sensitivities, and verify a response to antibiotic treatment. Cultures must be followed for at least six weeks.
If TB pericarditis is suspected, triple-drug therapy with isoniazid, rifampin, and streptomycin or ethambutol should be initiated and maintained for nine months. In addition, pyrazinamide should be administered for the first two months. Total treatment time can be shortened to six months if repeat cultures are negative.
Complications of TB pericarditis include caseous, hemorrhagic, and constrictive pericarditis. If treatment is delayed by two to four months, approximately 50% of patients will develop constrictive pericarditis. Corticosteroids should be administered for three months to minimize this complication. Even with aggressive antibiotic therapy nearly one third to one half of patients will require pericardiectomy, and of those approximately one third will die.
Most of the cardiac pathology associated with HIV involves the pericardium. Pericardial effusions, which are common, are usually small and asymptomatic, but their presence predicts a poorer prognosis at six months. Approximately 10% of pericardial effusions will progress to pericardial tamponade, requiring needle pericardiocentesis or surgical drainage. Because most pericardial effusions are due to TB and Mycobacterium avium intracellulare (MAI), an immediate evaluation for both organisms should be undertaken in cases of HIV pericarditis with symptomatic pericardial effusion.
Treatment of HIV pericarditis requires appropriate antiretroviral agents, protease inhibitors, and fusion inhibitors. Pertinent laboratory and imaging studies should be performed to rule out opportunistic infections, such as TB, MAI, Nocardia, and fungi as the cause. In addition, malignancies, especially Kaposi’s sarcoma and non-Hodgkin’s lymphoma, should be excluded.
CONSTRICTIVE PERICARDITIS: COMMON COMPLICATION
Constrictive pericarditis is a common complication of purulent pericarditis. The clinical manifestations of this complication are the result of chronic left and right heart congestion that elevates cardiac filling pressures and depresses cardiac output, resulting in systemic venous congestion. Thus, the characteristic appearance of patients with constrictive pericarditis is a swollen abdomen and edematous lower extremities that stand in stark contrast to a cachectic and wasted upper torso. In addition, distended jugular veins with a prominent Y descent is a classic clinical manifestation of constrictive pericarditis.
Signs and symptoms of left heart congestion include tachypnea, cough, exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Chronic fatigue and weakness result from low cardiac output and corresponding low blood pressure. On the other hand, chronic right heart congestion causes elevated venous pressures, which leads to jugular vein distension, ascites, and peripheral edema. Venous congestion of the gastrointestinal tract adversely affects the ability to absorb nutrients, precipitating weight loss and body wasting. Dyspepsia, anorexia, postprandial fullness, and increased abdominal girth are also common findings. Passive congestion of the liver leads to hepatomegaly and hepatic dysfunction.
Other physical findings in constrictive pericarditis include decreased pulse pressure, dullness in the base of the lungs due to pleural effusions, Kussmaul’s sign, and a pericardial knock. Kussmaul’s sign is loss of the normal inspiratory fall in jugular vein pressure with inspiration. In constrictive pericarditis, the jugular venous pulse increases with inspiration. A pericardial knock is an early diastolic sound heard best on inspiration. High-pitched and heard before the third heart sound, it is due to the abrupt halt of ventricular filling by the rigid pericardium.
LAB TESTS AND IMAGING STUDIES
Laboratory blood tests, an echocardiogram, ECG, chest x-ray, and pericardial fluid aspirate are essential in the clinical evaluation of pericarditis. In idiopathic pericarditis, the WBC count is minimally elevated. Viral titers are not helpful in the initial stages of pericarditis because they take days to weeks before increasing. On the other hand, the ESR is elevated in both viral and purulent pericarditis. Aspirated pericardial fluid should be cultured for viruses, bacteria, fungi, and mycobacteria and examined for tumor cells. Fungal and mycobacteria cultures may take six weeks or more before the organism can be identified. In some cases, the cultures may not produce any organisms. Connective tissue diseases should also be ruled out with antinuclear antibodies and rheumatoid factor tests.
The chest x-ray may be normal or may demonstrate cardiomegaly due to pericardial effusion. Pericardial effusion should be suspected when the cardiac silhouette enlarges in serial x-rays, especially if the lung fields remain clear. Chest x-rays may also reveal the cause of infectious pericarditis, such as pneumonia, empyema, or TB. Calcification of the pericardium suggests constrictive pericarditis.
The ECG usually demonstrates tachycardia. In addition, it typically shows several distinctive phases, which reflect the effects of pericardial inflammation on the epicardial surface of the heart. In phase 1, there is diffuse ST-segment elevation with upward concavity in all leads except aVR and V1 (see tracing below). ST- segment depression may be present in leads aVR and V1. PR-segment depression, which is characteristic of pericarditis, occurs in the limb leads. Reciprocal PR-segment elevation occurs in lead aVR. In phase 2, the ST and PR segments return to normal and the T waves flatten. In phase 3, the ST segments become isoelectric and diffuse T-wave inversion develops.
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If there is an associated pericardial effusion, the ECG may have low-voltage complexes, the result of the fluid interphase between the heart and the electrode. Electrical alternans, with alternating P wave, QRS complexes, and T waves, is due to the swinging of the heart in pericardial effusion. Atrial fibrillation may result from irritation of the atria by the inflamed pericardium.
The ECG changes associated with pericarditis can be differentiated from those of AMI. In pericarditis, the ST segments are elevated at the J point, are rarely greater than five millimeters, and retain their normal concavity. In AMI, they are typically dome-shaped but may maintain normal concavity. Furthermore, ST-segment elevations are diffuse in pericarditis, whereas in AMI they are limited to the anatomical area involved. Additionally, ST-segment elevation and T-wave inversion rarely occur simultaneously in pericarditis, and PR-segment depression is rarely seen outside of pericarditis. Sustained ventricular arrhythmias and QT prolongation are uncommon in pericarditis. Finally, the lack of reciprocal ST-segment changes and the absence of Q waves suggest pericarditis over AMI.
Echocardiography is used to evaluate the pericardium and pericardial space. It is the imaging study of choice to visualize pericardial effusion and pericardial tamponade. In most cases of pericarditis, the pericardium itself will appear normal. Thus, echocardiography is used mainly to visualize the pericardial effusion and display its volume, extent, and hemodynamic effect. In addition, it can show the heart swinging within the pericardial effusion. It assists in diagnosing pericardial tamponade by visualizing right atrial and ventricular collapse during diastole and a dilated inferior vena cava that does not collapse with inspiration.
Computed tomography can be used to diagnose pericarditis. It can demonstrate pericardial thickening associated with inflammation, pericardial effusions, and pericardial calcification associated with constrictive pericarditis. A CT scan is limited, however, by the need for contrast media, exposure to ionizing radiation, and difficulty differentiating intrapericardial fluid from a thickened pericardium. Magnetic resonance imaging (MRI) provides distinct anatomical detail of the pericardium and readily demonstrates pericardial effusions. However, it is inferior to CT in demonstrating pericardial calcification. The quality of this test is adversely affected by tachycardia and arrhythmias. Unlike CT scanning, MRI does not require contrast or exposure to ionizing radiation.
DISPOSITION OF PERICARDITIS
Because the most common cause of pericarditis is viral, the principal goal of treatment is usually to minimize the inflammatory process with the administration of nonsteroidal anti-inflammatory drugs (NSAIDs). High doses of NSAIDs typically suppress the clinical manifestations of pericarditis within 24 hours. Furthermore, unless purulent pericarditis is suspected, empiric antibiotics are not required. If NSAIDs are not effective, steroids can be administered for one to two weeks. If symptoms recur after steroids are tapered, the drugs can be readministered and maintained for one to two months with a gradual taper. In the case of multiple relapses despite steroids, immunosuppressive therapy may reduce the necessity for long-term steroid therapy. Idiopathic pericarditis recurs in approximately one third of cases. Direct pericardial biopsy may be needed for recurrent or persistent pericardial effusion.
Although infarction pericarditis is the result of inflammation, NSAIDs are not indicated. It has been demonstrated that these agents cause myocardial scar thinning and infarct expansion within the first week post-AMI. Instead, high-dose aspirin (up to 650 mg every four to six hours) should be prescribed. Colchicine and acetaminophen have also been recommended. On the other hand, NSAIDs are recommended for the treatment of Dressler’s syndrome, and oral steroids are indicated for refractory cases.
Management of purulent pericarditis is directed toward eradicating the specific causative organism and draining the purulent pericardial effusion. All patients with purulent pericarditis require admission to an ICU for observation, aggressive antibiotic therapy, and diagnostic and therapeutic pericardial drainage. Overall prognosis depends on the causative organism, response to treatment, and the severity of any complications that develop.
All patients with pericarditis require urgent cardiology consultation. Those with hemodynamically stable pericarditis should be admitted to telemetry.
In most cases, anticoagulants, which can precipitate intrapericardial hemorrhage and subsequent pericardial tamponade, should be avoided or discontinued. However, in AMI, anticoagulation may be used cautiously if combined with serial echocardiograms. Discontinuation of anticoagulation should be considered if echocardiography identifies a pericardial effusion greater than one centimeter in size. If pericardial tamponade develops, pericardiocentesis is essential.
Hemodynamically unstable pericardial tamponade that is unresponsive to pericardiocentesis requires immediate cardiothoracic surgery consultation for thoracotomy and pericardiotomy. Recurrent pericarditis usually requires pericardiectomy.
Suggested Reading
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Boltwood CM and Shah PM. The pericardium in health and disease. Curr Probl Cardiol 9(5):1, 1984.
Fowler NO: Tuberculous pericarditis. JAMA 266(1):99, 1991.
Gulteken F, et al.: Tuberculous pericarditis: a report of three cases. Curr Med Res Opin 17(2):142, 2001.
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Marrinella MA: Electrocardiographic manifestations and differential diagnosis of acute pericarditis. Am Fam Phys 57(4):699, 1998.
Martinez M and McKay M: Myocarditis and pericarditis. In Slaven E, et al. (eds): Infectious Diseases: Emergency Department Diagnosis and Management. McGraw-Hill, 2007.
Shabetai R and LeWinter MM: Pericardial complications of myocardial infarction. UpToDate 2006. Available at http://patients.uptodate.com/topic.asp?file=myoperic/4381. Accessed May 23, 2007.
Spodick DH: Acute pericarditis: current concepts and practice. JAMA 289(9):1150, 2003. |
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