INTRODUCTION
Normal pericardium consists of an outer sac, the fibrous pericardium; and an inner double-layered sac, the serous pericardium. The visceral layer of the serous pericardium, or epicardium, covers the heart and proximal great vessels. It is reflected to form the parietal pericardium, which lines the fibrous pericardium ( Fig. 24-1 ). The pericardium provides mechanical protection for the heart and lubrication to reduce friction between the heart and surrounding structures. The pericardium also has a significant hemodynamic impact on the atria and ventricles. The nondistendible pericardium limits acute distention of the heart (see Chapter 2 ).
Ventricular volume is greater at any given ventricular filling pressure with the pericardium removed than with the pericardium intact. The pericardium also contributes to diastolic coupling between two ventricles: The distention of one ventricle alters the filling of the other, an effect that is important in the pathophysiology of cardiac tamponade and constrictive pericarditis (CP). Ventricular interdependence within a normal pericardium is not noticeable clinically but becomes more marked when filling pressure becomes high or diastolic filling is limited. Among much pathology involving the pericardium, none is more fascinating than CP in terms of characteristic hemodynamics, clinical presentations, physical examination findings, and difficulty of diagnosis. This chapter will focus mainly on the underlying pathophysiology, clinical presentations, characteristic diagnostic features, various forms, and treatments of CP.
Acute accumulation of pericardial effusion results in sudden hemodynamic deterioration, as in cardiac rupture or hemopericardium. Detection of this acute cardiac tamponade is relatively easy by characteristic clinical setting (acute myocardial infarction, aortic dissection, or invasive cardiac procedure) and two-dimensional echocardiographic findings of hemopericardium. This entity is not discussed in this chapter. Subacute or chronic pericardial effusion may create prominent right-heart failure, the presentation of which may be similar to CP; and not infrequently, CP presents with varying degrees of pericardial effusion, including a presentation similar to cardiac tamponade, but hemo-dynamic abnormality persists after removal of pericardial effusion. This condition is called effusive-constrictive pericarditis and will be discussed at further length at the end of this chapter.
Interest in the pericardium dates back to antiquity. Hippocrates mentioned the “smooth mantle surrounding the heart and containing a small amount of fluid resembling urine.” In the 17th-century, a Cornish clinician, John Mayow, described the gross appearance of CP in his patient’s heart as “nearly covered by cartilage, adherent to its interior so that the blood could scarcely enter the ventricle,” illustrating diastolic filling abnormality of this disorder. Several hundred years passed before the first publication mentioning the hemodynamics of CP appeared in 1946 from New York University. Cournand and Richards, who received the Nobel Prize for their work on cardiac catheterization, described the pressure tracing of CP in a 30-year-old patient, resembling right ventricular (RV) failure with “certain additional features.” The additional features include normal ventricular systolic pressure, low ventricular pulse pressure, a marked elevation of mean atrial and ventricular diastolic pressure, and the prominence of early diastolic dip in atrial and ventricular pressure. At that time, the hemodynamics of restrictive cardiomyopathy (RC) were not firmly established, and subsequently it was recognized that the hemodynamic features of CP were similar to those of RC. Sixty years later, the same hemodynamic criteria are still being used in most cardiac catheterization laboratories to diagnose CP, although the criteria lack specificity. More insights into the pathophysiology and unique hemodynamic features of CP have established more specific diagnostic criteria for constriction, which can be demonstrated by noninvasive two-dimensional Doppler echocardiography, as well as by invasive cardiac hemodynamic measurements.
The diagnosis of CP is often overlooked, since ventricular systolic function is usually well preserved, and clinical manifestations can involve other organs, leading to investigation of noncardiac abnormalities before consideration of a pericardial disease. When discussing CP, it is impossible not to mention RC as well. Although CP and RC are two very different entities, they appear similar superficially. The hemodynamic end products of the constriction and restriction are almost identical, which makes their distinction difficult if not impossible by a casual inspection of a patient’s hemodynamic status. It is essential to demonstrate features unique to each condition and that are not present in other conditions. This chapter will, therefore, also describe the similarities and differences between constriction and restriction in their clinical characteristics, hemodynamic profiles, and laboratory data.
PATHOPHYSIOLOGY
CP is caused by noncompliant and usually (but not always) thickened pericardium ( Fig. 24-2 ). The pericardium becomes abnormal because of damage from inflammation, radiation, trauma, or an autoimmune process. A majority of patients with CP do have an underlying etiology, although this cannot be determined in a third of patients. In regions where tuberculosis is common, this is still the most frequent etiology for CP, but in the current era, previous cardiac surgery is the most common etiology in the United States, accounting for one third of surgically confirmed cases of CP, followed by acute pericarditis, radiation, and collagen vascular disease. Therefore, CP should always be considered if a patient presents with heart failure, normal ejection fraction, and history of one of the associated conditions. In CP, the atria and inferior vena cava are enlarged secondary to limited ventricular filling and high filling pressure. Ventricular septal thickness is not increased but shows a characteristic motion with respiratory septal shift.
Constrictive Pericarditis Versus Restrictive Cardiomyopathy
By definition, RC is a myocardial disease causing primarily diastolic dysfunction and heart failure similar to CP (see Chapter 21 ). RC can be idiopathic or secondary to infiltrative disease such as amyloidosis or sarcoidosis, or a storage disease such as Fabry’s disease. It has been also reported to occur secondary to hypereosinophilic syndrome, radiation, scleroderma, and medications such as chloroquine. Idiopathic or primary RC has distinct morphologic features that include nondilated, nonhypertrophied ventricles with biatrial enlargement (see Fig. 24-2B ). On the other hand, left ventricular (LV) wall thickness in secondary RC is usually increased, and there may be an overlap with the nonobstructive form of hypertrophic cardiomyopathy. Despite the different pathophysiologic mechanisms of CP and RC, they share many similar hemodynamic findings when measured by cardiac catheterization. Both have increased atrial pressures and equalization of end diastolic pressures although the equalization is more common in CP.
The “dip and plateau” pattern seen in ventricular diastolic pressure tracings has classically been associated with constriction. This finding, which reflects rapid early diastolic filling of the ventricles, followed by an abrupt cessation of filling in mid- and late diastole, is also found in RC, which is characterized by the noncompliant myocardium and limited ventricular filling during the mid- and late diastolic period. Therefore, there is a substantial overlap in hemodynamic features between CP and diastolic heart failure due to myocardial diseases. To distinguish one from the other condition, which is critical in providing an appropriate management, diagnostic features specific to a condition should be identified. There are two unique features in CP: (1) dissociation between intrathoracic and intracardiac pressures, which vary with respiration, and (2) increased interventricular coupling or dependence due to a relatively fixed combined volume of the left and right ventricles within the constrictive pericardium. These unique features result in characteristic respiratory variation in diastolic filling, ventricular pressures, and Doppler velocities representing diastolic filling.
Intrathoracic-Intracardiac Dissociation
The dissociation between intrathoracic and intracardiac pressures in constriction causes respiratory variation in pressure difference between pulmonary capillary wedge pressure (PCWP) and LV diastolic pressure. This characteristic hemodynamic pattern is best illustrated by simultaneous pressure recordings from the left ventricle and the pulmonary capillary wedge, together with mitral inflow velocities ( Fig. 24-3 ).
A thickened or inflamed pericardium prevents full transmission of the intrathoracic pressure changes that occur with respiration to the pericardial and intracardiac cavities, creating respiratory variations in the left-sided filling pressure gradient (the pressure difference between the pulmonary vein and the left atrium). With inspiration, intrathoracic pressure falls (3 to 5 mmHg normally), and the pressure in other intrathoracic structures (pulmonary vein, pulmonary capillaries) falls to a similar degree. This inspiratory pressure change is not fully transmitted to the intrapericardial and intracardiac cavities. As a result, the driving pressure gradient for LV filling decreases immediately after inspiration and increases with expiration.
Interventricular Dependence
Diastolic filling (or distensibility) of the left and right ventricles is interdependent because the overall cardiac volume is relatively fixed within the thickened or noncompliant (adherent) pericardium. Hence, reciprocal respiratory changes occur in the filling of both ventricles. With inspiration, decreased LV filling allows increased filling in the right ventricle. As a result, the ventricular septum shifts to the left, and tricuspid inflow E velocity and hepatic vein diastolic forward-flow velocity increase ( Fig. 24-4 ). With expiration, LV filling increases, causing the ventricular septum to shift to the right, which limits RV filling. Tricuspid inflow decreases and hepatic vein diastolic forward flow decreases, with increased flow reversals during diastole. Usually, diastolic forward-flow velocity is higher than systolic forward-flow velocity in the hepatic vein, which corresponds to the Y and X waves, respectively, of systemic venous pressure. It needs to be emphasized that the respiratory variation in ventricular filling is initiated from the left side, which is also evident from careful inspection of simultaneous pressure tracings from the left and right ventricles.
In CP, the fluctuation in the PCWP is more marked in parallel with intrathoracic pressure changes than fluctuation in left atrial (LA) and LV diastolic pressure. Ventricular interdependence also is observed in simultaneous recordings of LV and RV pressures. With inspiration, which induces less filling of the left ventricle, LV peak systolic pressure decreases; the opposite changes occur in the right ventricle, so that RV peak systolic pressure increases with inspiration. Their ejection time also varies with respiration in opposite directions in the left and right ventricles. This discordant pressure change between the ventricles in CP does not occur in RC ( Fig. 24-5 ).
Therefore, invasively or noninvasively, the diagnostic criteria of restriction and constriction should be based on the respiratory changes of ventricular filling and hemodynamic features instead of previously proposed criteria using the level of systolic RV pressure or equalization of ventricular end diastolic pressures, because there is a large overlap of the hemodynamic values between constriction and restriction. If cardiac catheterization is performed for evaluation of CP, the discordant respiratory change between RV and LV pressures during inspiration should be looked for as a sign of interdependence of ventricular filling.
Clinical Presentations and Physical Examination Findings
Clinical presentations of CP are protean and nonspecific, but almost all patients do have symptoms and signs of heart failure. Dyspnea, edema, ascites, and fatigue are common symptoms. Less common symptoms, but important to remember, are chest pain, gastrointestinal adversities, hypotension with tamponade (effusive-constrictive), arrhythmia, and right upper quadrant pain from hepatic congestion. Two thirds of the patients with CP do have an underlying etiology, as we have noted. On physical examination, jugular venous pressure (JVP) is almost always elevated with rapid “y” descent. However, JVP rises further with inspiration in CP (which is called Kussmaul sign ). Systemic and pulmonary venous congestion are parts of clinical presentations in both constriction and restriction. Ascites and hepatomegaly are more common in CP, and this may lead a physician to evaluate an abnormality in the liver or abdomen.
Among patients who were referred to our medical center and found to have CP, more than a third of them had undergone a gastrointestinal procedure or liver biopsy or sometimes both prior to their referral. If JVP is found to be elevated in patients with hepatomegaly or ascites, right-heart failure as an underlying cardiac abnormality, including CP, should be strongly considered. Pulsus paradoxus may be present in patients with CP but is less common than in cardiac tamponade. Pulmonary venous congestion is more common in RC than in CP, and this is a poor prognostic sign. Characteristically, a third heart sound is heard in both constriction and restriction, and it is difficult to distinguish them based on cardiac auscultation. The third heart sound corresponds to the time of the end of early rapid filling and the nadir of the “y” descent in atrial pressure tracings. In CP, this diastolic gallop sound is called a pericardial knock .
Electrocardiogram and Brain Natriuretic Peptide
Electrocardiography is nonspecific for both CP and RC, although low QRS voltage in the setting of increased LV wall thickness strongly suggests cardiac amyloidosis. Brain natriuretic peptide (BNP) is usually elevated in patients with RC and relatively normal in CP, especially when constriction is idiopathic ( Fig. 24-6 ). When constriction is related to coronary bypass surgery or radiation, BNP is higher than in idiopathic CP because of the underlying concomitant myocardial disease in those conditions. Therefore, relatively normal BNP in patients with clear evidence of heart failure suggests CP. The patients with cardiac amyloidosis usually have systemic amyloid with monoclonal gammopathy, positive fat aspirate, and other systemic manifestations of the disease. However, in a minority of patients, all these studies can be negative and may require RV endomyocardial biopsy for a definitive diagnosis.
Echocardiography
Two-Dimensional Echocardiography
Ventricular dimensions and ejection fractions are usually normal in both CP and RC. Ventricular wall thickness can be increased in some secondary forms of RC and markedly increased in the cases of infiltrative cardiomyopathy. The most common infiltrative cardiomyopathy is cardiac amyloid, but rare conditions such as glycogen storage disease, hyperoxalosis, and hydroxychloroquine myopathy should be considered. The RV wall thickness is also characteristically increased in most infiltrative cardiomyopathy.
When the myocardium is infiltrated by amyloid deposits, the valves, atrial wall, and ventricular walls are affected, providing a characteristic granular or speckled appearance on echocardiography. Other forms of secondary restrictive cardiomyopathy can also have characteristic echocardiographic features, such as areas of myocardial thinning or unusual regional wall motion abnormalities that do not follow a coronary distribution in sarcoidosis or apical endocardial thickening due to thrombus deposition in hypereosinophilic syndrome.
Ventricular septal motion is characteristically abnormal in patients with CP because of differential ventricular filling with respiration and increased interventricular dependence ( Fig. 24-7 ). Although the atria are generally larger in RC than in constriction, this feature cannot be used to differentiate one condition from the other. In RC, LA pressure is usually higher than right atrial (RA) pressure, and the atrial septum is curved toward the right atrium. The atrial septum has respiratory movement in patients with CP. The pericardial thickness is usually, but not always, increased in CP and can be measured by transthoracic and, better still, by transesophageal echocardiography (TEE). When calcified, it appears as a bright echo dense structure, and when inflamed with edema, it appears as a dark soft tissue or a rind. The inferior vena cava, hepatic vein, and pulmonary veins are dilated in both RC and CP, unless patients are well treated with a diuretic agent. In constriction, the atrioventricular groove may be indented with their characteristic appearance.
