Acute pericarditis, by far the most common pathologic process involving the pericardium (Table 28-1), has four principal diagnostic features:
Chest pain is usually present in acute infectious pericarditis and in many of the forms presumed to be related to hypersensitivity or autoimmunity. The pain of acute pericarditis is often severe, retrosternal, and left precordial, and referred to the neck, arms, or left shoulder. Frequently the pain is pleuritic, consequent to accompanying pleural inflammation (i.e., sharp and aggravated by inspiration and coughing), but sometimes it is steady, constricting, radiates into either arm or both arms, and resembles that of myocardial ischemia; therefore, confusion with acute myocardial infarction (AMI) is common. Characteristically, however, pericardial pain may be relieved by sitting up and leaning forward and is intensified by lying supine (Chap. 4). Pain is often absent in slowly developing tuberculous, postirradiation, and neoplastic, uremic, and constrictive pericarditis.
The differentiation of AMI from acute pericarditis may become perplexing when, with acute pericarditis, serum biomarkers of myocardial damage such as troponin and creatine kinase-MB rise, presumably because of concomitant involvement of the epicardium in the inflammatory process (an epi-myocarditis) with resulting myocyte necrosis. However, these elevations, if they occur, are quite modest given the extensive electrocardiographic ST-segment elevation in pericarditis. This dissociation is useful in differentiating between these conditions.
A pericardial friction rub is audible at some point in about 85% of patients with acute pericarditis, may have up to three components per cardiac cycle, is high-pitched, and is described as rasping, scratching, or grating (Chap. 9). It is heard most frequently at end expiration with the patient upright and leaning forward.
The electrocardiogram (ECG) in acute pericarditis without massive effusion usually displays changes secondary to acute subepicardial inflammation (Fig. 28-1). It typically evolves through four stages. In stage 1, there is widespread elevation of the ST segments, often with upward concavity, involving two or three standard limb leads and V2 to V6, with reciprocal depressions only in aVR and sometimes V1. Also, there is depression of the PR segment below the TP segment, reflecting atrial involvement. Usually there are no significant changes in QRS complexes. After several days, the ST segments return to normal (stage 2), and only then, or even later, do the T waves become inverted (stage 3). Weeks or months after the onset of acute pericarditis, the ECG returns to normal (stage 4). In contrast, in AMI, ST elevations are convex, and reciprocal depression is usually more prominent; these changes may return to normal within a day or two. Q waves may develop, with loss of R-wave amplitude, and T-wave inversions are usually seen within hours before the ST segments have become isoelectric (Chaps. 40 and 41).
Pericardial effusion is usually associated with pain and/or the ECG changes mentioned above, as well as electrical alternans. Pericardial effusion is especially important clinically when it develops within a relatively short time because it may lead to cardiac tamponade (see below). Differentiation from cardiac enlargement may be difficult on physical examination, but heart sounds may be fainter with pericardial effusion. The friction rub and the apex impulse may disappear. The base of the left lung may be compressed by pericardial fluid, producing Ewart’s sign, a patch of dullness and increased fremitus (and egophony) beneath the angle of the left scapula. The chest roentgenogram may show enlargement of the cardiac silhouette, with a “water bottle” configuration, but may be normal.
Acute pericarditis. There are diffuse ST-segment elevations (in this case in leads I, II, aVF, and V2 to V6) due to a ventricular current of injury. There is PR-segment deviation (opposite in polarity to the ST segment) due to a concomitant atrial injury current.
Two-dimensional echocardiogram in lateral view in a patient with a large pericardial effusion. Ao, aorta; LV, left ventricle; pe, pericardial effusion; RV, right ventricle. (From M Imazio: Curr Opin Cardiol 27:308, 2012.)
TABLE 28-1CLASSIFICATION OF PERICARDITIS ||Download (.pdf) TABLE 28-1 CLASSIFICATION OF PERICARDITIS
|CLINICAL CLASSIFICATION |
|I. Acute pericarditis (<6 weeks) |
| A. Fibrinous |
| B. Effusive (serous or sanguineous) |
|II. Subacute pericarditis (6 weeks to 6 months) |
| A. Effusive-constrictive |
| B. Constrictive |
|III. Chronic pericarditis (>6 months) |
| A. Constrictive |
| B. Effusive |
| C. Adhesive (nonconstrictive) |
|Etiologic Classification |
|I. Infectious pericarditis |
| A. Viral (coxsackievirus A and B, echovirus, mumps, adenovirus, hepatitis, HIV) |
| B. Pyogenic (pneumococcus, Streptococcus, Staphylococcus, Neisseria, Legionella) |
| C. Tuberculous |
| D. Fungal (histoplasmosis, coccidioidomycosis, Candida, blastomycosis) |
| E. Other infections (syphilitic, protozoal, parasitic) |
|II. Noninfectious pericarditis |
| A. Acute myocardial infarction |
| B. Uremia |
| C. Neoplasia |
| 1. Primary tumors (benign or malignant, mesothelioma) |
| 2. Tumors metastatic to pericardium (lung and breast cancer, lymphoma, leukemia) |
| D. Myxedema |
| E. Cholesterol |
| F. Chylopericardium |
| G. Trauma |
| 1. Penetrating chest wall |
| 2. Nonpenetrating |
| H. Aortic dissection (with leakage into pericardial sac) |
| I. Postirradiation |
| J. Familial Mediterranean fever |
| K. Familial pericarditis |
| 1. Mulibrey nanisma |
| L. Acute idiopathic |
| M. Whipple’s disease |
| N. Sarcoidosis |
|III. Pericarditis presumably related to hypersensitivity or autoimmunity |
| A. Rheumatic fever |
| B. Collagen vascular disease (systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, scleroderma, acute rheumatic fever, granulomatosis with polyangiitis [Wegener’s]) |
| C. Drug-induced (e.g., procainamide, hydralazine, phenytoin, isoniazid, minoxidil, anticoagulants, methysergide) |
| D. Postcardiac injury |
| 1. Postmyocardial infarction (Dressler’s syndrome) |
| 2. Postpericardiotomy |
| 3. Posttraumatic |
Echocardiography (Chap. 12) is the most widely used imaging technique. It is sensitive, specific, simple, noninvasive, may be performed at the bedside, and can identify accompanying cardiac tamponade (see below) (Fig. 28-2). The presence of pericardial fluid is recorded by two-dimensional transthoracic echocardiography as a relatively echo-free space between the posterior pericardium and left ventricular epicardium in patients with small effusions and as a space between the anterior right ventricle and the parietal pericardium just beneath the anterior chest wall. In patients with large effusions, the heart may swing freely within the pericardial sac. When severe, the extent of this motion alternates and may be associated with electrical alternans (Fig. 28-3). Echocardiography allows localization and identification of the quantity of pericardial fluid.
Electrical alternans. This tracing was obtained from a patient with a large pericardial effusion with tamponade. (Reproduced from DM Mirvis, AL Goldberger: Electrocardiography, in RO Bonow et al [eds]: Braunwald’s Heart Disease, 9th ed. Philadelphia: Elsevier, 2012.)
The diagnosis of pericardial fluid or thickening may be confirmed by computed tomography (CT) or magnetic resonance imaging (MRI). These techniques may be superior to echocardiography in detecting loculated pericardial effusions, pericardial thickening, and the identification of pericardial masses.
TREATMENT Acute Pericarditis
There is no specific therapy for acute idiopathic pericarditis, but bed rest and anti-inflammatory treatment with aspirin (2–4 g/d), with gastric protection (e.g., omeprazole 20 mg/d), may be given. If this is ineffective, one of the nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (400–600 mg tid) or indomethacin (25–50 mg tid), should be tried. In responsive patients, these doses should be continued for 1–2 weeks and then tapered over several weeks. In patients who are unresponsive, colchicine (0.5 mg bid, given for 4–8 weeks) has been found to be effective, not only in acute pericarditis, but also in reducing the risk of recurrent pericarditis. Colchicine is concentrated in and interferes with the migration of neutrophils, is contraindicated in patients with hepatic or renal dysfunction, and may cause diarrhea and other gastrointestinal side effects. Glucocorticoids (e.g., prednisone 1 mg/kg per day) usually suppress the clinical manifestations of acute pericarditis in patients who have failed therapy with the anti-inflammatory therapies described above, but appear to increase the risk of subsequent recurrence. Therefore, full-dose corticosteroids should be given for only 2–4 days and then tapered. Anticoagulants should be avoided because their use could cause bleeding into the pericardial cavity and tamponade.
In patients with recurrences that are multiple, frequent, disabling, continue for more than 2 years, and are not prevented by colchicine and other NSAIDs and are not controlled by glucocorticoids, pericardial stripping may be necessary to terminate the illness, and usually does so.
The accumulation of fluid in the pericardial space in a quantity sufficient to cause serious obstruction of the inflow of blood into the ventricles results in cardiac tamponade. This complication may be fatal if it is not recognized and treated promptly. The most common causes of tamponade are idiopathic pericarditis and pericarditis secondary to neoplastic disease. Tamponade may also result from bleeding into the pericardial space after leakage from an aortic dissection, cardiac operations, trauma, and treatment of patients with acute pericarditis with anticoagulants.
The three principal features of tamponade (Beck’s triad) are hypotension, soft or absent heart sounds, and jugular venous distention with a prominent x descent but an absent y descent. The limitations of ventricular filling are responsible for a reduction of cardiac output. The quantity of fluid necessary to produce cardiac tamponade may be as small as 200 mL when the fluid develops rapidly to as much as >2000 mL in slowly developing effusions when the pericardium has had the opportunity to stretch and adapt to an increasing volume. Tamponade may also develop more slowly, and in these circumstances, the clinical manifestations can resemble those of heart failure, including dyspnea, orthopnea, and hepatic engorgement.
A high index of suspicion for cardiac tamponade is required because in many instances no obvious cause for pericardial disease is apparent, and this diagnosis should be considered in any patient with otherwise unexplained enlargement of the cardiac silhouette, hypotension, and elevation of jugular venous pressure. There may be reduction in amplitude of the QRS complexes, and electrical alternans of the P, QRS, or T waves should raise the suspicion of cardiac tamponade (Fig. 28-3).
Table 28-2 lists the features that distinguish acute cardiac tamponade from constrictive pericarditis.
TABLE 28-2FEATURES THAT DISTINGUISH CARDIAC TAMPONADE FROM CONSTRICTIVE PERICARDITIS AND SIMILAR CLINICAL DISORDERS ||Download (.pdf) TABLE 28-2 FEATURES THAT DISTINGUISH CARDIAC TAMPONADE FROM CONSTRICTIVE PERICARDITIS AND SIMILAR CLINICAL DISORDERS
|CHARACTERISTIC ||TAMPONADE ||CONSTRICTIVE PERICARDITIS ||RESTRICTIVE CARDIOMYOPATHY ||RVMI ||EFFUSIVE CONSTRICTIVE PERICARDITIS |
|Clinical || || || || || |
|Pulsus paradoxus ||+++ ||+ ||+ ||+ ||+++ |
|Jugular veins || || || || || |
|Prominent y descent ||– ||++ ||+ ||+ ||– |
|Prominent x descent ||+++ ||++ ||+++ ||+ ||+++ |
|Kussmaul’s sign ||– ||+++ ||+ ||+++ ||++ |
|Third heart sound ||– ||– ||+ ||+ ||+ |
|Pericardial knock ||– ||++ ||– ||– ||– |
|Electrocardiogram || || || || || |
|Low ECG voltage ||++ ||++ ||++ ||– ||++ |
|Electrical alternans ||++ ||– ||– ||– ||+ |
|Echocardiogram || || || || || |
|Thickened pericardium ||– ||+++ ||– ||– ||++ |
|Pericardial calcification ||– ||++ ||– ||– || |
|Pericardial effusion ||+++ ||– ||– ||++ || |
|RV size ||Usually small ||Usually normal ||Usually normal ||Enlarged || |
|RA and RV ||+++ ||– ||– ||– || |
|Exaggerated respiratory variation in flow velocity ||+++ ||+++ ||– ||+++ || |
|CT/MRI || || || || || |
|Thickened pericardium ||– ||+++ ||– ||++ || |
|Cardiac catheterization || || || || || |
|Equalization of diastolic pressures ||+++ ||+++ ||– ||++ || |
This important clue to the presence of cardiac tamponade consists of a greater than normal (10 mmHg) inspiratory decline in systolic arterial pressure. When severe, it may be detected by palpating weakness or disappearance of the arterial pulse during inspiration, but usually sphygmomanometric measurement of systolic pressure during slow respiration is required.
Because both ventricles share a tight incompressible covering, i.e., the pericardial sac, the inspiratory enlargement of the right ventricle in cardiac tamponade compresses and reduces left ventricular volume; leftward bulging of the interventricular septum reduces further the left ventricular cavity as the right ventricle enlarges during inspiration. Thus, in cardiac tamponade, the normal inspiratory augmentation of right ventricular volume causes an exaggerated reduction of left ventricular volume, stroke volume, and systolic pressure. Paradoxical pulse also occurs in approximately one-third of patients with constrictive pericarditis (see below), and in some cases of hypovolemic shock, acute and chronic obstructive airway disease, and pulmonary embolus. Right ventricular infarction (Chap. 41) may resemble cardiac tamponade with hypotension, elevated jugular venous pressure, an absent y descent in the jugular venous pulse, and, occasionally, a paradoxical pulse (Table 28-2).
Low-pressure tamponade refers to mild tamponade in which the intrapericardial pressure is increased from its slightly subatmospheric levels to +5 to +10 mmHg; in some instances, hypovolemia coexists. As a consequence, the central venous pressure is normal or only slightly elevated, whereas arterial pressure is unaffected and there is no paradoxical pulse. These patients are asymptomatic or complain of mild weakness and dyspnea. The diagnosis is aided by echocardiography, and both hemodynamic and clinical manifestations improve after pericardiocentesis.
Because immediate treatment of cardiac tamponade may be lifesaving, prompt measures to establish the diagnosis by echocardiography should be undertaken. When pericardial effusion causes tamponade, Doppler ultrasound shows that tricuspid and pulmonic valve flow velocities increase markedly during inspiration, whereas pulmonic vein, mitral, and aortic flow velocities diminish (as in constrictive pericarditis, see below) (Fig. 28-4). In tamponade, there is late diastolic inward motion (collapse) of the right ventricular free wall and the right atrium. Transesophageal echocardiography, CT, or cardiac MRI may be necessary to diagnose a loculated effusion responsible for cardiac tamponade.
TREATMENT Cardiac Tamponade
Patients with acute pericarditis should be observed frequently for the development of an effusion; if a large effusion is present, pericardiocentesis should be carried out or the patient watched closely for signs of tamponade. Arterial and venous pressures should be monitored and serial echocardiograms obtained. PERICARDIOCENTESIS
If manifestations of tamponade appear, echocardiographically guided pericardiocentesis using an apical, parasternal, or, most commonly, subxiphoid approach must be carried out at once because reduction of the elevated intrapericardial pressure may be lifesaving. Intravenous saline may be administered as the patient is being readied for the procedure, but the pericardiocentesis must not be delayed. If possible, intrapericardial pressure should be measured before fluid is withdrawn, and the pericardial cavity should be drained as completely as possible. A small, multiholed catheter advanced over the needle inserted into the pericardial cavity may be left in place to allow draining of the pericardial space if fluid reaccumulates. Surgical drainage through a limited (subxiphoid) thoracotomy may be required in recurrent tamponade, when it is necessary to remove loculated effusions, and/or when it is necessary to obtain tissue for diagnosis.
Pericardial fluid obtained from an effusion often has the physical characteristics of an exudate. Bloody fluid is most commonly due to neoplasm, renal failure, or dialysis in the United States and tuberculosis in developing nations but may also be found in the effusion of acute rheumatic fever, after cardiac injury, and after myocardial infarction. Transudative pericardial effusions may occur in heart failure.
The pericardial fluid should be analyzed for red and white blood cells and cytologic studies, and cultures should be obtained. The presence of DNA of Mycobacterium tuberculosis determined by the polymerase chain reaction strongly supports the diagnosis of tuberculous pericarditis.
VIRAL OR IDIOPATHIC ACUTE PERICARDITIS
In many instances, acute pericarditis occurs in association with illnesses of known or presumed viral origin and probably is caused by the same agent. Commonly, there is an antecedent infection of the respiratory tract, and viral isolation and serologic studies are negative. In some cases, coxsackievirus A or B or the virus of influenza, echovirus, mumps, herpes simplex, chickenpox, adenovirus, or cytomegalovirus has been isolated from pericardial fluid and/or appropriate elevations in viral antibody titers have been noted. Pericardial effusion is a common cardiac manifestation of HIV; it is usually secondary to infection (often mycobacterial) or neoplasm, most often lymphoma. Frequently, a viral cause cannot be established, and the term idiopathic acute pericarditis is then appropriate.
Viral or idiopathic acute pericarditis occurs at all ages but is more common in young adults and is often associated with pleural effusions and pneumonitis. The almost simultaneous development of fever and precordial pain, often 10–12 days after a presumed viral illness, constitutes an important feature in the differentiation of acute pericarditis from AMI, in which chest pain precedes fever. The constitutional symptoms are usually mild to moderate, and a pericardial friction rub is often audible. The disease ordinarily runs its course in a few days to 4 weeks. The ST-segment alterations in the ECG usually disappear after 1 or more weeks, but the abnormal T waves may persist for several years and be a source of confusion in persons without a clear history of pericarditis. Pleuritis and pneumonitis frequently accompany viral or idiopathic acute pericarditis. Accumulation of some pericardial fluid is common, and both tamponade and constrictive pericarditis are possible, but infrequent, complications.
The most frequent complication is recurrent (relapsing) pericarditis, which occurs in about one-fourth of patients with acute idiopathic pericarditis. In a smaller number, there are multiple recurrences. For treatment, see earlier section on treatment of acute pericarditis.
Postcardiac injury syndrome
Acute pericarditis may appear in a variety of circumstances that have one common feature—previous injury to the myocardium with blood in the pericardial cavity. The syndrome may develop after a cardiac operation (postpericardiotomy syndrome), after blunt or penetrating cardiac trauma (Chap. 29), or after perforation of the heart with a catheter. Rarely, it follows AMI.
The clinical picture mimics acute viral or idiopathic pericarditis. The principal symptom is the pain of acute pericarditis, which usually develops 1–4 weeks after the cardiac injury but earlier (1–3 days) after AMI. Recurrences are common and may occur up to 2 years or more following the injury. Fever, pleuritis, and pneumonitis are the outstanding features, and the bout of illness usually subsides in 1 or 2 weeks. The pericarditis may be of the fibrinous variety, or it may be a pericardial effusion, which is often serosanguineous but rarely causes tamponade. ECG changes typical of acute pericarditis may also occur. This syndrome is probably the result of a hypersensitivity reaction to antigen(s) that originate from injured myocardial tissue and/or pericardium.
Often no treatment is necessary aside from aspirin and analgesics. When the illness is severe or followed by a series of disabling recurrences, therapy with an NSAID, colchicine, or a glucocorticoid, such as described for treatment of acute pericarditis, is usually effective.
Because there is no specific test for acute idiopathic pericarditis, the diagnosis is one of exclusion. Consequently, all other disorders that may be associated with acute fibrinous pericarditis must be considered. A common diagnostic error is mistaking acute viral or idiopathic pericarditis for AMI and vice versa. When acute fibrinous pericarditis is associated with AMI (Chap. 41), it is characterized by fever, pain, and a friction rub in the first 4 days after the development of the infarct. ECG abnormalities (such as the appearance of Q waves, brief ST-segment elevations with reciprocal changes, and earlier T-wave changes in AMI) and the extent of the elevations of markers of myocardial necrosis (higher in AMI) are helpful in differentiating pericarditis from AMI.
Pericarditis secondary to postcardiac injury is differentiated from acute idiopathic pericarditis chiefly by timing. If it occurs within a few days or weeks of an AMI, a chest blow, a cardiac perforation, or a cardiac operation, it may be justified to conclude that the two are probably related.
It is important to distinguish pericarditis due to collagen vascular disease from acute idiopathic pericarditis. Most important in the differential diagnosis is the pericarditis due to systemic lupus erythematosus (SLE) or drug-induced (procainamide or hydralazine) lupus. When pericarditis occurs in the absence of any obvious underlying disorder, the diagnosis of SLE may be suggested by a rise in the titer of antinuclear antibodies. Acute pericarditis is an occasional complication of rheumatoid arthritis, scleroderma, and polyarteritis nodosa, and other evidence of these diseases is usually obvious.
Pyogenic (purulent) pericarditis is usually secondary to cardiothoracic operations, by extension of infection from the lungs or pleural cavities, from rupture of the esophagus into the pericardial sac, or from rupture of a ring abscess in a patient with infective endocarditis. It may also complicate the viral, pyogenic, mycobacterial, and fungal infections that occur with HIV infection. It is generally accompanied by fever, chills, septicemia, and evidence of infection elsewhere and generally has a poor prognosis. The diagnosis is made by examination of the pericardial fluid. It requires drainage as well as vigorous antibiotic treatment.
Pericarditis of renal failure occurs in up to one-third of patients with chronic uremia (uremic pericarditis), and is also seen in patients undergoing chronic dialysis who have normal levels of blood urea and creatinine (dialysis-associated pericarditis). These two forms of pericarditis may be fibrinous and are generally associated with serosanguineous effusions. A pericardial friction rub is common, but pain is usually absent or mild. Treatment with an NSAID and intensification of dialysis are usually adequate. Occasionally, tamponade occurs and pericardiocentesis is required. When the pericarditis of renal failure is recurrent or persistent, a pericardial window should be created or pericardiectomy may be necessary.
Pericarditis due to neoplastic diseases results from extension or invasion of metastatic tumors (most commonly carcinoma of the lung and breast, malignant melanoma, lymphoma, and leukemia) to the pericardium; pain, atrial arrhythmias, and tamponade are complications that occur occasionally. Diagnosis is made by pericardial fluid cytology or pericardial biopsy. Mediastinal irradiation for neoplasm may cause acute pericarditis and/or chronic constrictive pericarditis. Unusual causes of acute pericarditis include syphilis, fungal infection (histoplasmosis, blastomycosis, aspergillosis, and candidiasis), and parasitic infestation (amebiasis, toxoplasmosis, echinococcosis, and trichinosis).
CHRONIC PERICARDIAL EFFUSIONS
Chronic pericardial effusions are sometimes encountered in patients without an antecedent history of acute pericarditis. They may cause few symptoms per se, and their presence may be detected by finding an enlarged cardiac silhouette on a chest roentgenogram. Tuberculosis is a common cause. Myxedema may be responsible for chronic pericardial effusion that is sometimes massive but rarely, if ever, causes cardiac tamponade. The cardiac silhouette may be markedly enlarged, and an echocardiogram distinguishes cardiomegaly from pericardial effusion. The diagnosis of myxedema can be confirmed by tests of thyroid function. Myxedematous pericardial effusion responds to thyroid hormone replacement. Neoplasms, SLE, rheumatoid arthritis, mycotic infections, radiation therapy to the chest, pyogenic infections, and chylopericardium may also cause chronic pericardial effusion and should be considered and specifically sought in such patients.
Aspiration and analysis of the pericardial fluid are often helpful in diagnosis. Pericardial fluid should be analyzed as described in pericardiocentesis. Grossly sanguineous pericardial fluid results most commonly from a neoplasm, tuberculosis, renal failure, or slow leakage from an aortic dissection. Pericardiocentesis may resolve large effusions, but pericardiectomy may be required in patients with recurrence. Intrapericardial instillation of sclerosing agents may be used to prevent reaccumulation of fluid.