Pericardial diseases constitute pathologic processes that involve the pericardium, the pericardial sac and its contents, and the thoracic structures surrounding the heart. Cardiovascular perturbations associated with pericardial disease range from the asymptomatic electrocardiographic findings in uremic pericarditis to catastrophic circulatory collapse observed in the setting of acute hemorrhagic pericardial tamponade. The clinical features of pericardial diseases may resemble right-side failure, notably right ventricular (RV) failure and tricuspid insufficiency, but can also present as left-side failure manifesting as shortness of breath, reduced exercise tolerance, and multiorgan hypoperfusion. However, clinical management of pericardial pathology may differ significantly from that of ventricular dysfunction or valvular heart disease. As a consequence, timely diagnosis and initiation of appropriate medical or surgical therapy is imperative. This chapter deals specifically with the clinical utility of transesophageal echocardiography (TEE) in the evaluation, diagnosis, and characterization of pericardial disease including constrictive pericarditis and cardiac tamponade.

The pericardium consists of three layers: a fibrous layer that blends with the adventitia of the great vessels and systemic and pulmonary venous inflows, a parietal layer lining the inner surface of the fibrous pericardium, and a visceral layer lining the epicardium.1 The visceral component is made up of a single layer of mesothelial cells, is attached to the surface of the heart and epicardial fat, and regulates the production of pericardial fluid (normally 5 to 30 mL may be seen in the pericardial space).2 This layer also reflects back on itself to line the outer fibrous layer forming the parietal pericardium.1 The latter is composed of collagen fibers meshed with elastic fibers that allow considerable flexibility of the pericardium during childhood and early adult years, although this elasticity is lost with advancing age. The pericardial space conforms to the shape of the heart, and extends superiorly for a short distance along the great vessels to form a small pocket posteriorly, known as the transverse sinus. Similarly, the oblique sinus is formed by an extension of the pericardium posterior to the left atrium between the pulmonary veins. The function of the pericardium includes protection of the heart from the spread of infection or malignancy from surrounding structures, reduction of friction between the heart and the adjacent tissues, control of hydrostatic forces on the heart, prevention of acute chamber dilatation, and maintenance of diastolic coupling between the ventricles.2

Despite its ability to isolate the heart from direct extension of infectious and noninfectious pathogens, pericardial inflammation occurs in nearly 5% of the population according to autopsy findings, but is clinically detected in fewer than 0.1% of hospital admissions.3 The causes of pericarditis are numerous: idiopathic, infectious (viral, tuberculosis, acute bacterial, fungal, toxoplasmosis, or amebiasis), acute myocardial infarction, uremia, neoplastic disease, radiation, autoimmune (acute rheumatic fever, systemic lupus erythematosus, or rheumatoid arthritis), sarcoidosis, amyloidosis, drugs (hydralazine, procainamide, phenytoin, or penicillin), trauma, postcardiotomy for cardiac surgery, dissecting aortic aneurysm, myxedema, and chylopericardium.4 Most cases tend to be idiopathic or viral in origin and produce pathologic findings consistent with acute inflammation. These findings include infiltration with lymphocytes, polymorphonuclear neutrophils, and macrophages; alterations in pericardial vascularity; deposition of fibrin; and increase in pericardial fluid content that, depending on the rate of accumulation and the amount of exudate fluid within the pericardial sac, can result in clinical features of cardiac tamponade.5 Following the acute inflammatory phase, fibrous adhesions may be present between the pericardium and the epicardium, pleura, sternum, and any other tissues contiguous with the pericardium.6 In constrictive pericarditis the two pericardial layers are not necessarily thickened, but they are always fused together. As the pericardial compliance decreases, increases in tissue oxygen demand can be met only by increases in heart rate because stroke volume is fixed or progressively declining.

The symptomatology associated with constrictive pericarditis is dependent on the cause and severity of acute pericarditis, the degree of progression to chronic constrictive pericarditis, and the limitation to chamber filling. Most often, patients complain of retrosternal chest pain that is extremely variable in intensity and quality and may be suggestive of acute abdomen or myocardial ischemia. Frequently, patients find relief by sitting up and bending forward. In contrast, lying supine, coughing, or deep breathing exacerbates the pain. Notable findings on physical examination include a pericardial rub, distant heart sounds, increased jugular venous pressure, edema, ascites, and Kussmaul’s sign (increased right atrial pressure with inspiration resulting in a paradoxical elevation in jugular venous distention). The physical findings often are indistinguishable from those of severe RV dysfunction and tricuspid insufficiency: liver congestion, abdominal ascites, and lower extremity edema. The electrocardiogram typically demonstrates diffuse ST-segment concave elevation (without reciprocal ST-segment depression as seen in myocardial ischemia). However, these ST changes are detected primarily during the early stages of pericarditis. In addition, the electrocardiogram may have a low-voltage pattern. In chronic pericarditis, the chest radiographs may show calcification of the pericardium principally on lateral views with a normal cardiac silhouette, or there may be evidence of cardiomegaly (Figure 15–1). In addition, large pleural effusions may be seen.

In constrictive pericarditis, the diastolic filling is impaired, and the total cardiac volume is decreased. Ventricular and atrial volume changes are governed by the noncompliant pericardium, not by the compliance of the chambers. Because of the pericardial constriction, ventricular filling is characterized by an early rapid increase in diastolic pressure such that the pressure gradient between atrium and ventricle dissipates abruptly and filling terminates (plateaus) in early diastole. On a ventricular pressure waveform, this characteristic finding of constrictive pericarditis is referred to as the dip and plateau or square-root sign (Figure 15–2).7–11 Similarly, recording of the central venous tracing exhibits the classic “M” or “W” pattern in which the V wave is enhanced secondary to noncompliance of the atrium arising from pericardial constraint.7,8 Increased right atrial (RA) pressures also lead to a rapid y descent, reflecting abrupt emptying of the atrium with tricuspid valve opening. In all, the prominent features of constrictive pericarditis include a fused pericardium, a relatively fixed intracardiac volume, and equalization of diastolic chamber pressures. That is, the central venous pressure (CVP) equalizes with the RA pressure, the RV end-diastolic pressure, the left atrial (LA) pressure, and the left ventricular (LV) end-diastolic pressure, or its surrogate, the pulmonary artery occlusion pressure (PAOP).

Two-Dimensional Echocardiography

The echocardiographic assessment of thickened pericardium by the transthoracic approach is often limited and is diagnostic in less than one-third of cases of constrictive pericarditis. In contrast, two-dimensional TEE examination can identify pericardial thickening in constrictive pericarditis in nearly 90% of cases.12 A comprehensive TEE approach has the advantage of better image resolution and enhanced definition of the pericardial interface with fat, fluid, and surrounding tissue that is comparable to ultrafast computer tomography and magnetic resonance imaging techniques (Figure 15–3).13,14 Normally, the pericardium is an echo-dense line, 1 to 2 mm in thickness, separated from the myocardium by an area of lucency (fluid or pericardial fat). Pericardial thickening appears as increased echogenicity on two-dimensional echo and as multiple parallel reflections at the surface of the LV on M-mode.

Midesophageal (ME) four-chamber, ME two-chamber, ME long-axis (LAX), deep transgastric, and transgastric short-axis views allow for imaging of LV and RV walls and surrounding pericardium. The pericardium should be examined for echo-density, homogeneity, and thickening. Thickness of the pericardium is measured from the outer border of the myocardium to the outer edge of the pericardium, avoiding areas of echolucent space between the two borders, with a pericardium thicker than 3 mm considered abnormal.15,16 Multiple measurements should be performed to obtain an average thickness, and multiple views of the pericardium should be imaged because pericardial thickening may be asymmetric in distribution. This heterogeneity of pericardial involvement accounts for some of the limitations in diagnosing and detecting pericardial disease when using TTE. Additional features of the echocardiographic examination that assist in the diagnosis of constrictive pericarditis include abnormal interventricular septal motion (see below) and atrial compression by the thickened pericardium.

Examination of the venous inflow to the right and left heart (vena cava and pulmonary veins) also may assist in the diagnosis of pericardial disease. As previously described, by advancing the probe to the ME depth and optimizing the view of LA and RA separated by the interatrial septum, the bicaval view can be imaged by rotating the multiplane angle forward to 90°. The inferior vena cava (IVC) will appear on the top left of the screen as it enters the atrium. Maintaining this view while advancing the probe more distally into the esophagus will demonstrate the entire length of the IVC and the intrahepatic veins as they enter the IVC. A dilated and nonpulsatile IVC is a nonspecific indicator of constrictive pericarditis.7 Moreover, a decrease with spontaneous inspiration in IVC diameter of less than 50% at the junction of the RA is a marker of elevated RA pressure. Similarly, variations in pulmonary vein flow velocities with respiration (see below) aid in the diagnosis of constriction.

M-mode

On TTE M-mode echocardiography, diagnostic features in constrictive pericarditis, include pericardial thickening, flattening of the LV inferolateral wall during mid- to late diastole, LA enlargement, abnormal diastolic and systolic motions of the interventricular septum, atrial systolic notch (a posterior rather than the normal anterior interventricular septal motion occurring after the onset of electrocardiographic P wave that terminates before the QRS complex), and premature pulmonic valve closure.17 Diastolic septal motion is related primarily to the trans-septal pressure gradient, which in constrictive pericarditis is derived from the abrupt filling of the ventricles. Therefore, during the early phase of diastole, the interventricular septum can exhibit a sudden posterior deflection followed by a more gradual posterior septal motion occurring later in diastole (atrial systolic notch). Whereas these findings may be apparent in constrictive pericarditis, Engel and associates reported a low sensitivity in the diagnosis of constrictive pericarditis with the use of M-mode.17 In a series of 40 patients with a diagnosis of constrictive pericarditis confirmed by hemodynamic criteria, surgical examination, or necropsy, the most common findings by M-mode were abnormal septal motion and flattening of the LV inferolateral wall motion in diastole.17 However, posterior septal motion abnormality is seen in other pathologic states including RV volume overload, ischemic heart disease, and in the setting of cardiac surgery. Although the use of M-mode may have limitations in the assessment of constrictive pericarditis, in general, all patients with this pathology will display abnormal findings on M-mode. Thus, M-mode should be considered an adjunct to other modalities of echocardiographic diagnosis of constrictive pericarditis.

Pulsed-Wave Doppler

Doppler examination of flow dynamics is often diagnostic of constrictive pericarditis and is an important adjunct in differentiating pericardial processes from myocardial pathology associated with diastolic dysfunction. The Doppler findings characterize the flow dynamics due to the rigid, noncompliant pericardium encompassing both ventricles, minimizing their diastolic volume, exaggerating their interdependence, and isolating them from intrathoracic respiratory changes. RV and LV diastolic inflow velocities show high early inflow velocities (E wave) consistent with rapid early filling and rapid equalization of pressures. This is a reflection of the restraining effect of the thickened pericardium and of the decreased filling of the ventricles in mid- to late diastole. The mitral and tricuspid late inflow velocities (A wave) are extremely low or virtually absent, as in a restrictive filling pattern, with the atrial contraction contributing little to LV filling. In addition, the deceleration time of the E velocity is short.

In constrictive pericarditis, pulmonary vein flow dynamics should correlate with the expected findings of pericardial impediment of atrial filling during ventricular systole (blunting of the S wave), followed by relatively larger diastolic flow (D wave). Although the D wave is greater in magnitude than the S, it also becomes limited by poor chamber compliance during the latter part of diastole as ventricular pressure rapidly equilibrates with atrial pressure. Consequently, atrial contraction will have little to no contribution to ventricular filling, resulting in redirection of blood flow from the atrium to the pulmonary vein depicted as a larger A wave.18 However, the clinical validity of Doppler findings is highly dependent on the ultrasonographer’s technical expertise, the clinical setting at the time of the examination (ie, loading conditions), and, more importantly, its confirmation or support of other clinical or echocardiographic correlates of the underlying pathophysiology.

The aforementioned findings are highly influenced by respiratory variations and by ventricular interaction (please refer to the Cardiac Tamponade section for additional details). Normally, decreases in intrathoracic pressure with spontaneous inhalation are transmitted to the heart and the pulmonary veins. In healthy, spontaneously ventilating subjects, this decreased intrathoracic pressure results in minor decreases in pulmonary vein to LA pressure gradient, resulting in mild decrease in LV filling (<10% to 15% fluctuation of the mitral inflow E wave).19 In constrictive pericarditis, the thickened pericardium isolates the intrapericardial cardiac chambers (but not the extrapericardially located pulmonary veins) from changes in intrathoracic pressure during the respiratory cycle. As a result, mitral inflow E and pulmonary vein D velocities decrease during inspiration. This decrease in diastolic flow is due to a significant decrease in the pressure gradient between the pulmonary vein and the LA. During spontaneous exhalation, mitral inflow E and pulmonary vein D velocities increase (>25% compared with the inspiratory values) as intrathoracic pressure rises and the flow of blood previously pooled in the lungs during inspiration increases.20,21 Reciprocal changes are seen on the right side of the heart such that RV filling increases with spontaneous inspiration and decreases with exhalation. A variation greater than 25% between inspiratory and expiratory velocities on the right side is also indicative of constrictive pericarditis. In addition, prominent hepatic vein diastolic flow reversal may be noticed as a result of increased RA pressure.

As compared with spontaneous breathing, positive pressure ventilation reverses the respiratory variation of mitral inflow and pulmonary vein inflow velocities in subjects with constrictive pericarditis.22 Relative to exhalation, a mechanical breath increases the intrathoracic pressure, leading to greater mitral inflow E and pulmonary vein D velocities during Doppler examination.

Increased respiratory variation in mitral inflow E velocities in conjunction with pulmonary vein inflow velocity variation is virtually pathognomonic for constrictive pericarditis (Figure 15–4).7 This is an important finding that helps to distinguish constrictive pericarditis from restrictive cardiomyopathy in which there is no respiratory variation in velocities, as well as no pericardial thickening. Of note, there is a subset of patients with constrictive pericarditis who do not exhibit respiratory variation, namely those with atrial fibrillation or severely elevated LA pressures.