Chapter 265: Pericardial Disease

The normal pericardium is a double-layered sac; the visceral pericardium is a serous membrane that is separated from the fibrous parietal pericardium by a small quantity (15–50 mL) of fluid, an ultrafiltrate of plasma. The normal pericardium, by exerting a restraining force, prevents sudden dilation of the cardiac chambers, especially the right atrium and ventricle, during exercise and with hypervolemia. It also restricts the anatomic position of the heart, and probably retards the spread of infections from the lungs and pleural cavities to the heart. Nevertheless, total absence of the pericardium, either congenital or after surgery, does not produce obvious clinical disease. In partial left pericardial defects, the main pulmonary artery and left atrium may bulge through the defect; very rarely, herniation and subsequent strangulation of the left atrium may cause sudden death.

Acute pericarditis, by far the most common pathologic process involving the pericardium (Table 265-1), has four principal diagnostic features:

1. Chest pain is usually present in acute infectious pericarditis and in many of the forms presumed to be related to hypersensitivity, autoimmunity, or of unknown cause (idiopathic). The pain of acute pericarditis is often severe, retrosternal and/or 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, radiates to the trapezius ridge, or into either arm, and resembles that of myocardial ischemia; therefore, confusion with acute myocardial infarction (AMI) is common. Characteristically, pericardial pain may be intensified by lying supine, and relieved by sitting up and leaning forward (Chap. 11). Pain is often absent in slowly developing tuberculous, postirradiation, neoplastic, and uremic pericarditis.

   The differentiation of AMI from acute pericarditis may be challenging when, with the latter, 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 compared to those in AMI, given the extensive electrocardiographic ST-segment elevation in pericarditis. This dissociation is useful in differentiating between these conditions.

2. A pericardial friction rub is audible at some point in the illness in about 85% of patients with acute pericarditis, it may have up to three components per cardiac cycle, is rasping, scratching, or grating (Chap. 234). It is heard most frequently at end expiration with the patient upright and leaning forward.

3. The electrocardiogram (ECG) in acute pericarditis without massive effusion usually displays changes secondary to acute subepicardial inflammation (Fig. 265-1A). 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–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, unless a large pericardial effusion develops (see below). 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 upwardly 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; these changes are usually seen within hours before the ST segments have become isoelectric (Chaps. 268 and 269).

4. Pericardial effusion is usually associated with pain and/or the ECG changes mentioned above, and if the effusion is large with electrical alternans (Fig. 265-1B). 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 on physical examination may be difficult, but heart sounds may be fainter with large 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 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 in patients with small effusions.

Diagnosis

Echocardiography (Chap. 236) is the most widely used imaging technique. It is sensitive, specific, simple, noninvasive, may be performed at the bedside, and allows localization and estimation of the quantity of pericardial fluid. 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 and/or as a space between the anterior right ventricle and the parietal pericardium just beneath the anterior chest wall (Fig. 265-2).

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. MRI is also helpful in detecting pericardial inflammation (Fig. 265-3).

TREATMENT

CARDIAC TAMPONADE

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, tuberculosis, or bleeding into the pericardial space after leakage from an aortic dissection, cardiac operation, trauma, and treatment 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 (early systolic) descent but an absent y (early diastolic) descent. The limitations to ventricular filling are responsible for reductions of cardiac output and arterial pressure. 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.

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 sudden enlargement of the cardiac silhouette, hypotension, and elevation of jugular venous pressure. There also may be reductions in amplitude of the QRS complexes, and electrical alternans of the P, QRS, or T waves should raise the suspicion of cardiac tamponade (Fig. 265-1).

Table 265-2 lists the features that distinguish acute cardiac tamponade from constrictive pericarditis.

Paradoxical Pulse

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 even 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 causes leftward bulging of the interventricular septum, compresses and reduces left ventricular volume; stroke volume, and arterial 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 embolism. Right ventricular infarction (Chap. 269) 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 265-2).

Diagnosis

Because immediate treatment of cardiac tamponade may be lifesaving, prompt establishment of the diagnosis, usually 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. 265-4). 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

VIRAL OR IDIOPATHIC ACUTE PERICARDITIS

In many instances, acute pericarditis occurs in association with or following illnesses of known or presumed viral origin and probably is caused by the same agent. There may be an antecedent infection of the respiratory tract, but viral isolation and serologic studies are usually 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 observed. Frequently, a viral cause cannot be established, and the term idiopathic acute pericarditis is appropriate.

Viral or idiopathic acute pericarditis occurs at all ages but is most common in young adult males, and is often associated with pleural effusion 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. Elevations of C-reactive protein and of the white blood cell count are common. 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. 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.

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. S8), 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. Recurrences are common and may occur up to 2 years or more following the injury. Fever, pleuritis, and pneumonitis are accompanying features, and the 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 and 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 another NSAID, colchicine, or a glucocorticoid, such as described for treatment of acute pericarditis, is usually effective.

DIFFERENTIAL DIAGNOSIS

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.

Pericarditis secondary to postcardiac injury is differentiated from acute idiopathic pericarditis chiefly by timing. If it occurs within a few days or weeks of a chest blow, a cardiac perforation, a cardiac operation, or an AMI, 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; Chap. 349) 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 valvular ring abscess in a patient with infective endocarditis. It may also complicate the viral, bacterial, 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 immediate drainage as well as vigorous antibiotic treatment.

Pericarditis of renal failure (uremic pericarditis) occurs in up to one-third of patients with severe renal dysfunction, and is also seen in patients undergoing chronic dialysis who have normal levels of blood urea (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. The pain of pericarditis, tamponade, and atrial arrhythmias 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) (Table 265-1).

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 and myxedema may be causal. Neoplasms, SLE, rheumatoid arthritis, mycotic infections, radiation therapy to the chest, 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 under 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.

This disorder results when the healing of an acute fibrinous or serofibrinous pericarditis or the resorption of a chronic pericardial effusion is followed by obliteration of the pericardial cavity with the formation of granulation tissue. The latter gradually contracts and forms a firm scar encasing the heart, which may become calcified. In developing nations, a high percentage of cases are of tuberculous origin, but this is now an uncommon cause in North America or Western Europe. Chronic constrictive pericarditis may follow acute or relapsing viral or idiopathic pericarditis, trauma with organized blood clot, or cardiac surgery of any type, or results from mediastinal irradiation, purulent infection, histoplasmosis, neoplastic disease (especially breast cancer, lung cancer, and lymphoma), rheumatoid arthritis, SLE, or chronic renal failure treated by chronic dialysis. In many patients, the cause of the pericardial disease is undetermined, and in these patients an asymptomatic or forgotten bout of viral pericarditis, idiopathic or acute, may have been the inciting event.

The basic physiologic abnormality in patients with chronic constrictive pericarditis is the inability of the ventricles to fill because of the limitations imposed by the rigid, thickened pericardium. Ventricular filling is unimpeded during early diastole but is reduced abruptly when the elastic limit of the pericardium is reached, whereas in cardiac tamponade, ventricular filling is impeded throughout diastole. In both conditions, ventricular end-diastolic and stroke volumes are reduced and the end-diastolic pressures in both ventricles and the mean pressures in the atria, pulmonary veins, and systemic veins are all elevated to similar levels (i.e., within 5 mmHg of one another). Despite these hemodynamic changes, systolic function may be normal or only slightly impaired at rest. However, in advanced cases, the fibrotic process may extend into the myocardium and cause myocardial scarring and atrophy, and venous congestion may then be due to the combined effects of the pericardial and myocardial lesions.

In constrictive pericarditis, the right and left atrial pressure pulses display an M-shaped contour, with prominent x and y descents. The y descent, which is absent or diminished in cardiac tamponade, is the most prominent deflection in constrictive pericarditis; it reflects rapid early filling of the ventricles. The y descent is interrupted by a rapid rise in atrial pressure during early diastole, when ventricular filling is impeded by the constricting pericardium. These characteristic changes are transmitted to the jugular veins, where they may be recognized by inspection. In constrictive pericarditis, the ventricular pressure pulses in both ventricles exhibit characteristic “square root” signs during diastole. These hemodynamic changes, although characteristic, are not pathognomonic of constrictive pericarditis and may also be observed in restrictive cardiomyopathies (Chap. 254, Table 254-2).

CLINICAL AND LABORATORY FINDINGS

Weakness, fatigue, weight gain, increased abdominal girth, abdominal discomfort, and edema are common. The patient often appears chronically ill, and in advanced cases, anasarca, skeletal muscle wasting, and cachexia may be present. Exertional dyspnea is common, and orthopnea may occur, although it is usually not severe. The cervical veins are distended and may remain so even after intensive diuretic treatment, and venous pressure may fail to decline during inspiration (Kussmaul’s sign). The latter is common in chronic pericarditis but may also occur in tricuspid stenosis, right ventricular infarction, and restrictive cardiomyopathy.

The pulse pressure is normal or reduced. A paradoxical pulse can be detected in about one-third of cases. Congestive hepatomegaly is pronounced and may impair hepatic function and cause jaundice; ascites is common and is usually more prominent than dependent edema. Pleural effusions and splenomegaly may also be present. The apical pulse is reduced and may retract in systole (Broadbent’s sign). The heart sounds may be distant; an early third heart sound (i.e., a pericardial knock) occurring at the cardiac apex with the abrupt cessation of ventricular filling is often conspicuous.

The ECG frequently displays low voltage of the QRS complexes and diffuse flattening or inversion of the T waves. Atrial fibrillation is present in about one-third of patients. The chest roentgenogram shows a normal or slightly enlarged heart. Pericardial calcification is most common in tuberculous pericarditis. Pericardial calcification may, however, occur in the absence of constriction, and constriction may occur without calcification.

Inasmuch as the common physical signs of cardiac disease (murmurs, cardiac enlargement) may be inconspicuous or absent in chronic constrictive pericarditis, hepatic enlargement, and dysfunction associated with jaundice and intractable ascites may lead to a mistaken diagnosis of hepatic cirrhosis. This error can be avoided if the neck veins are inspected and found to be distended.

The transthoracic echocardiogram often shows pericardial thickening, dilation of the inferior vena cava and hepatic veins, and a sharp halt to rapid left ventricular filling in early diastole, with normal ventricular systolic function and flattening of the left ventricular posterior wall. There is a distinctive pattern of transvalvular flow velocity on Doppler echocardiography (Fig. 265-4). During inspiration, there is an exaggerated reduction in blood flow velocity in the pulmonary veins and across the mitral valve and a leftward shift of the ventricular septum; the opposite occurs during expiration. Diastolic flow velocity in the inferior vena cava into the right atrium and across the tricuspid valve increases in an exaggerated manner during inspiration and declines during expiration. However, echocardiography cannot definitively establish or exclude the diagnosis of constrictive pericarditis; CT and MRI are more accurate, the latter is useful in evaluating myocardial involvement.

DIFFERENTIAL DIAGNOSIS

Like chronic constrictive pericarditis, cor pulmonale (Chap. 252) may be associated with marked systemic venous hypertension, little pulmonary congestion, a heart that is not enlarged, and a paradoxical pulse. However, in cor pulmonale, advanced parenchymal pulmonary disease is usually apparent and venous pressure falls during inspiration (i.e., Kussmaul’s sign is negative). Tricuspid stenosis (Chap. 261) may also simulate chronic constrictive pericarditis with congestive hepatomegaly, splenomegaly, ascites, and venous distention. However, the characteristic murmur and that of accompanying mitral stenosis are usually present.

Because it can be corrected surgically, it is important to distinguish chronic constrictive pericarditis from restrictive cardiomyopathy (Chap. 254), which has a similar physiologic abnormality (i.e., restriction of ventricular filling). The differentiating features are summarized in Table 265-2. When a patient has progressive, disabling, and unresponsive congestive heart failure and displays any of the features of constrictive heart disease, Doppler echocardiography to record respiratory effects on transvalvular flow (Fig. 265-4) and an MRI or CT scan should be obtained to detect or exclude constrictive pericarditis, because the latter is usually correctable.

TREATMENT

Subacute Effusive-Constrictive Pericarditis

This form of pericardial disease is characterized by the combination of a tense effusion in the pericardial space and constriction of the heart by thickened pericardium. As such, it shares a number of features with both chronic pericardial effusion producing cardiac compression and with pericardial constriction. It may be caused by tuberculosis (see below), multiple attacks of acute idiopathic pericarditis, radiation, traumatic pericarditis, renal failure, scleroderma, and neoplasms. The heart is generally enlarged, and a paradoxical pulse is usually present. After pericardiocentesis, the physiologic findings may change from those of cardiac tamponade to those of pericardial constriction. Furthermore, the intrapericardial pressure and the central venous pressure may decline, but not to normal. The diagnosis can be established by pericardiocentesis followed by pericardial biopsy. Wide excision of both the visceral and parietal pericardium is usually effective therapy.

Tuberculous Pericardial Disease

This chronic infection is a common cause of chronic pericardial effusion, especially in the developing world where active tuberculosis and HIV are endemic. Tuberculous pericarditis may present as pericardial effusion, chronic constrictive pericarditis, or subacute effusive constrictive pericarditis (see above). The clinical picture is that of a chronic, systemic illness in a patient with pericardial effusion. It is important to consider this diagnosis in a patient with known tuberculosis, with HIV, and with fever, chest pain, weight loss, and enlargement of the cardiac silhouette of undetermined origin. If the etiology of chronic pericardial effusion remains obscure despite detailed analysis including culture of the pericardial fluid, a pericardial biopsy, preferably by a limited thoracotomy, should be performed. If definitive evidence is still lacking but the specimen shows granulomas with caseation, antituberculous chemotherapy (Chap. 173) is indicated.

If the biopsy specimen shows a thickened pericardium after 2–4 weeks of antituberculous therapy, pericardiectomy should be carried out to prevent the development of constriction. Tubercular cardiac constriction should be treated surgically while the patient is receiving antituberculous chemotherapy.