Pathophysiology of the Pericardium

Pathophysiology of the Pericardium

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PR O G RE S S I N C ARDI O V A S CU L A R D I S EA S E S 5 9 (2 0 1 7) 34 1–3 4 8

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Pathophysiology of the Pericardium Brian D. Hoit ⁎ Physiology and Biophysics, Case Western Reserve University, Cleveland, OH University Hospitals Cleveland Medical Center, Cleveland, OH

A R T I C LE I N F O

AB ST R A C T

Keywords:

Pericardial heart disease includes pericarditis, (an acute, subacute, or chronic fibrinous,

Pressure–volume relations

noneffusive, or exudative process), and its complications, constriction, (an acute, subacute,

Heart failure

or chronic adhesive or fibrocalcific response), and cardiac tamponade. The pathophysiology

Cardiac tamponade

of cardiac tamponade and constrictive pericarditis readily explains their respective findings

Constrictive pericarditis

on clinical examination, Doppler echocardiography, and at cardiac catheterization. The primary abnormality of cardiac tamponade is pan-cyclic compression of the cardiac chambers by increased pericardial fluid requiring that cardiac chambers compete for a fixed intrapericardial volume. Features responsible for the pathophysiology include transmission of thoracic pressure through the pericardium and heightened ventricular interdependence. Constrictive pericarditis is a condition in which the pericardium limits diastolic filling and causes dissociation of intracardiac and intrathoracic pressures, and heightened ventricular interdependence. Both conditions result in diastolic dysfunction, elevated and equal venous and ventricular diastolic pressure, respiratory variation in ventricular filling, and ultimately, reduced cardiac output. © 2016 Elsevier Inc. All rights reserved.

Contents Physiology of the pericardium . . . . . . . . . . . . . . . . . . . . Pathophysiology of the pericardium . . . . . . . . . . . . . . . . . Pathophysiologic role of pericardium in HF . . . . . . . . . . . Pathophysiology of post-cardiac injury syndrome . . . . . . . Pathophysiology of pericardial effusion and cardiac tamponade Pathophysiology of constrictive pericarditis . . . . . . . . . . . Comparison with cardiac tamponade . . . . . . . . . . . . Comparison with restrictive cardiomyopathy . . . . . . . . Pathophysiology of effusive-constrictive pericarditis . . . . . . Statement of Conflict of Interest . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Statement of Conflict of Interest: see page 347. ⁎ Address reprint requests to Brian D. Hoit, MD, Harrington Heart & Vascular Center, University Hospitals Cleveland Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106-5038. E-mail address: [email protected] http://dx.doi.org/10.1016/j.pcad.2016.11.001 0033-0620/© 2016 Elsevier Inc. All rights reserved.

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Abbreviations and Acronyms CO = cardiac output

Physiology of the pericardium

HF = heart failure

The pericardium is composed of visceral and parietal compoLV = left ventricle or ventricular nents. The visceral RA = right atrium or atrial pericardium is a mesothelial monolayer that RV = right ventricle or ventricular adheres firmly to the epicardium, reflects over the origin of the great vessels, and becomes the serosal layer of the parietal pericardium, a tough, fibrous tissue which envelops the heart. The pericardial space is enclosed between these two serosal layers and normally contains up to 50 mL of plasma ultrafiltrate. This thin layer of pericardial fluid reduces friction on the epicardium and equalizes gravitational, hydrostatic, and inertial forces over the surface of the heart, so that transmural cardiac pressures neither change during acceleration nor differ regionally within cardiac chambers. The mesothelium of the pericardium is metabolically active and produces endothelin, prostaglandin E2, eicosanoids, and prostacyclin, which modulate sympathetic neurotransmission and myocardial contractility, and may influence epicardial coronary arterial tone.1,2 In addition to immunologic and fibrinolytic activities of the pericardium, the level of brain natriuretic peptide in the pericardial fluid is a sensitive and accurate indicator of ventricular volume and pressure and may play an autocrine–paracrine role in heart failure (HF).3 Pericardial reflections around the great vessels tether the pericardium superiorly and result in the formation of the oblique sinus (a midline cul-de-sac between the pulmonary veins and inferior vena cava), the transverse sinus (a tunnel-like passageway between the great vessels and the atria and veins) and its extensions, the pericardial recesses. These potential spaces are major contributors to the pericardial reserve volume, the difference between unstressed pericardial volume and cardiac volume that accommodates physiological LA = left atrium or atrial

Table 1 – Functions of the pericardium. Mechanical Limits short-term cardiac distention Facilitates cardiac chamber coupling and interaction Maintains pressure–volume relations of the cardiac chambers and their output Membranous/Serosal Lubricates, reduces friction Equalizes gravitational, hydrostatic, and inertial forces Mechanical barrier to infection Metabolic Immunologic Vasomotor Fibrinolytic Modulates sympathetic neurotransmission and contractility Ligamentous Limits displacement of the heart Neutralizes the effects of respiration and change of body position Contributes to apparent compliance of the pericardium

changes in ventricular filling. Superior and inferior pericardiosternal and diaphragmatic ligaments limit displacement of the pericardium and its contents within the chest and neutralize the effects of respiration and change of body position.4 In addition, these attachments contribute to the apparent compliance of the pericardial pressure–volume relation.5 Histologically, the pericardium is composed predominantly of compact collagen layers interspersed with short elastin fibers. The abundance and orientation of the collagen fibers are responsible for the characteristic viscoelastic mechanical properties of the pericardium, stress relaxation and creep (the former substantial, the latter insignificant in humans), and hysteresis.6 The pericardium is not essential for life and no adverse consequences follow congenital absence or surgical removal of the pericardium. However, the pericardium serves important albeit subtle functions (Table 1). Once pericardial reserve volume is spent, the pericardium limits distension of the cardiac chambers and facilitates interaction and coupling of the ventricles and atria.6 Limitation of cardiac filling volumes by the pericardium may also limit cardiac output (CO) and oxygen delivery during exercise; it was shown that removing the pericardium of greyhound dogs caused a 25% increase in VO2max and CO.7 The pericardium also influences quantitative and qualitative aspects of ventricular filling, i.e., the thin-walled right ventricle (RV) and atrium are more subject to the influence of the pericardium than is the more resistant, thick-walled left ventricle (LV)8 and after removal of the pericardium, the early to late diastolic velocity (E/A) ratio increases across the mitral valve and decreases across the tricuspid valve, a response which may be explained by the differences between right atrial (RA) and left atrial (LA) compliances.9 Surprisingly, the manner in which pericardial pressure should be measured remains an unresolved dilemma. In the absence of a pericardial effusion, determining pericardial pressure with a fluid-filled catheter may be inappropriate since the pericardial “cavity” is largely a potential space. When incised, the normal parietal pericardium retracts, indicating that the pericardium exerts a constitutive stress on the underlying myocardium (termed an epicardial radial stress) and it has been argued that contact force using a flat gas or liquid-filled unstressed balloons be used to measure pericardial constraint.10 Indeed, pressures measured with flat balloons are essentially the same as the theoretical pericardial pressure (i.e., the fall of LV diastolic pressure upon widely opening the pericardium when measured at the same LV volume) in the absence of a pericardial effusion.10 Although it is generally assumed that except for hydrostatic difference, conventional pericardial pressure over the cardiac surface is uniform, it cannot be assumed apriori that pericardial contact pressure (the normal force exerted by the pericardium per unit area of balloon) is uniform over the heart. In fact, using flat, air-filled balloons, we showed that pericardial contact pressure is greater over the left than right heart, increasing over the LV with aortic compression and volume loading and increasing over the RV with pulmonary artery compression and volume loading.11,12 While these concepts have

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Fig 1 – Pericardial pressure–volume curves from a rapidly developing (left) and more slowly developing (right) effusion. The flat, initial segment of the curves is the pericardial reserve volume that once exceeded, causes a steep increase in pressure (Fig 16 JASE 2013;26:965–1012). Reproduced with permission from Klein et al.4 important implications for normal pericardial physiology, in cardiac tamponade, conventional fluid-filled pressures are appropriate, and in constrictive pericarditis, obliteration of the pericardial space makes evaluating pericardial pressure moot. Although the magnitude and importance of pericardial restraint of ventricular filling at physiologic cardiac volumes are controversial, there is general agreement that the pericardial reserve volume is relatively small and that pericardial influences become significant when the reserve volume is exhausted. This may occur with rapid increases in blood volume and in disease states characterized by rapid increases in heart size (e.g., acute mitral and tricuspid regurgitation, pulmonary embolism, RV infarction). The pressure–volume relation of the pericardium is nonlinear; i.e., the relation is initially flat (producing little to no change in pressure for changes in volume) and when the pericardial reserve volume is outstripped, develops a “bend” or “knee” and terminates in a steep slope (producing large changes in pressure for small changes in volume) (Fig 1). Thus acutely, relatively small pericardial effusions may cause cardiac tamponade. In contrast, chronic stretching of the pericardium results in “stress relaxation”, pericardial hypertrophy and a rightward shift of the pressure–volume relation, which explains why large but slowly developing effusions may not produce tamponade (Fig 1). A discussion of pericardial physiology would be incomplete without passing mention of other important pericardial functions, namely, preventing excessive torsion and displacement of the heart, minimizing friction with surrounding structures, and serving as an anatomic barrier to the spread of infection from contiguous structures (Table 1).

Pathophysiology of the pericardium In view of the pericardium's simple structure, clinicopathologic processes involving it are understandably few, and the

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response to injury is limited to exudation of fluid, fibrin and inflammatory cells. Healing may result in obliteration of the pericardial space by adhesions between the visceral and parietal layers and later calcification, either focal or extensive, may occur. Accordingly, pericardial heart disease includes only pericarditis, which may be an acute, subacute, or chronic fibrinous, “noneffusive,” or exudative process; and its complications, tamponade and its variants; and constriction, which may be an acute, subacute, or chronic adhesive or fibrocalcific response (Fig 2). However, despite a limited number of clinical syndromes, the pericardium is affected by virtually every category of disease, including infectious, neoplastic, immune–inflammatory, metabolic, iatrogenic, traumatic, and congenital etiologies.

Pathophysiologic role of pericardium in HF Acute HF and volume overload increase pericardial restraint once the pericardial reserve volume is surpassed; when this occurs, a significant proportion of the increase in ventricular diastolic pressure is shouldered by the pericardium. In hemodynamic terms, transmural distending pressure in a cardiac chamber is less than intracavitary pressures recorded with a catheter in that chamber. To appreciate the role that the pericardium plays in the pathophysiology of chronic heart failure, it is necessary to make use of the concepts of pericardial restraint and ventricular interaction, pericardial pressure–volume and stress–strain relations, the nature and measurement of pericardial pressure, and LV diastolic pressure–volume relationships. Hemodynamic studies of vasodilators in acute decompensated HF using high fidelity pressure manometry and ventriculography serendipitously demonstrated that the pericardium contributed significantly to the observed elevations of LV diastolic pressure.13 The venodilator nitroglycerine, which decreased ventricular volume, shifted the entire diastolic LV pressure–volume relation downward, whereas the arteriolar dilator amyl nitrate, which had little effect on LV volume, lowered pressure along the trajectory of the initial pressure–volume curve. In chronically instrumented dogs,14 rapid volume (dextran) infusion shifted the entire diastolic pressure–segment length relation upward (and increased conventionally-measured pericardial pressure), which subsequently fell with nitroprusside infusion (Fig 3A). After recovery from pericardiectomy, dextran infusion increased ventricular diastolic pressure, but simply added higher pressure points along the same curve (rather than shifting the entire curve upward), and nitroprusside lowered pressure by adding lower points along the same curve (rather than shifting the entire curve downward). When pericardial pressure was subtracted from the ventricular diastolic pressure before pericardiectomy, the curves were similar to those obtained after pericardiectomy (Fig 3B). In another set of chronically instrumented canine experiments, infrarenal aorto-caval anastomoses were constructed and the effect of pericardiectomy on the diastolic pressure-segment length curve over a wide range of LV diastolic volumes was examined acutely (3 days) and after several weeks of shunting.15 Acutely, the pressure–segment

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Fig 2 – Gross pathology of the pericardium. (A) Diffuse fibrin deposits over the visceral and parietal pericardium (fibrinous pericarditis) as seen in uremia. (B) Fibrinohemorrhagic exudate commonly associated with neoplasms. (C) Fibrous pericarditis with thickened visceral and parietal pericardia resulting in constriction, as may be seen in radiation pericarditis. Note the fibrous adhesions between parietal pericardium and mediastinal and lung pleura. Reproduced with permission from Klein et al.4

length curve shifted to the right after pericardiectomy, but chronically, the rightward shift upon opening the pericardium was abrogated, indicating the loss of pericardial restraint and reduced ventricular interaction; this could be accounted for by chronic volume overload causing an increase in pericardial chamber compliance. This change in compliance was later shown in vitro with biaxial stretching of the pericardium and measurement of stress–strain curves to be due to a change in the biomechanical properties of the pericardial tissue itself.16

Pathophysiology of post-cardiac injury syndrome The post-cardiac injury syndrome (postmyocardial infarction syndrome, postpericardiotomy syndrome, posttraumatic pericarditis) is initiated by the combination of damage to mesothelial pericardial cells and blood in the pericardial space.17 The initial injury is thought to release cardiac antigens and stimulate an immune response. The immune complexes that are generated deposit in the pericardium, pleura, and lungs, and elicit an inflammatory response.7 Observations consistent with this pathogenesis include the discrete latent period from cardiac injury to the clinical onset of the syndrome (primarily pericarditis), coexistent pleural effusions and pulmonary infiltrates, significant correlations between the postoperative to preoperative ratios of anti-actin and -myosin antibodies, the clinical occurrence of the post-cardiac injury syndrome in patients undergoing cardiac surgery,18,19 the generally excellent response to antiinflammatory therapy, and the occasional relapse that occurs after steroid withdrawal. However, the significance of autoantibodies and their relation to the severity of myocardial injury are not firmly established20 and it has been suggested that the antibodies represent an epiphenomenon.21 In addition, the occurrence of the post-cardiac injury syndrome in

immunosuppressed children following orthotopic cardiac transplant22 suggests that the syndrome is not always an autoimmune process.

Pathophysiology of pericardial effusion and cardiac tamponade The clinical presentations of patients with pericardial effusion are diverse and depend on the volume of the effusion and its rate of accumulation, the nature and etiology of the effusion (e.g., effusion owing to neoplasm, chronic hemodialysis, tuberculosis, and radiation have a greater tendency to develop tamponade), the thickness and compliance of the pericardium, and the presence of co-existing heart disease. Cardiac tamponade is a hemodynamic condition characterized by equal elevation of atrial and pericardial pressures, an exaggerated expiratory decrease in aortic systolic pressure (pulsus paradoxus) and arterial hypotension. The pathophysiology of cardiac tamponade and pulsus paradoxus readily explains findings on clinical examination, Doppler echocardiography, and at cardiac catheterization. The primary abnormality is compression of the cardiac chambers due to increased pericardial pressure that is exerted throughout the cardiac cycle.23 The pericardium has some degree of elasticity (part of the pericardial reserve volume) but once the elastic limit is reached, the heart must compete with the intrapericardial fluid for a fixed intrapericardial volume. As the total pericardial volume reaches the stiff portion of its pressure–volume relation, tamponade rapidly ensues and as cardiac tamponade progresses, the cardiac chambers become smaller, and diastolic chamber compliance is reduced. Very little fluid needs to accumulate to produce cardiac tamponade once the pericardium can no longer stretch.23 At this point, the initial removal of fluid during pericardiocentesis produces the greatest reduction in intrapericardial pressure.

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of another chamber, and (3) that total cardiac volume (and therefore total pericardial volume) is minimal during ventricular ejection, venous return is progressively shifted to systole as cardiac tamponade becomes more severe. In early tamponade, venous return is maintained by venoconstriction and salt and water retention. However, when cardiac tamponade is severe, total venous return falls, the cardiac chambers get smaller, and CO and blood pressure fall. Another important consequence of constrained cardiac filling and ventricular interdependence is the characteristic respiratory variation in venous return and transvalvular flows. The inspiratory decline in thoracic pressure is transmitted through the pericardium to the right side of the heart and the pulmonary vasculature and as a result, systemic venous return to the right heart increases and pulmonary venous return to the left heart decreases with inspiration. In cardiac tamponade, the constraining pericardium prevents the free wall from expanding and the ensuing distension of the RV is limited to the interventricular septum; coupled with relative underfilling of the LV, the septum to bulges the left, reducing LV compliance and contributing to further decreased filling of the LV during inspiration. With expiration, the opposite changes occur and LV filling preferentially follows. Ventricular interaction (or interdependence) is the principal mechanism responsible for pulsus paradoxus, a hallmark of cardiac tamponade (Fig 4). Pulsus paradoxus will occur once pericardial pressure becomes substantially higher than ventricular diastolic pressures; however, in less severe disease, the degree to which it occurs is related in part to the rate of pericardial fluid accumulation and to pericardial compliance, both of which are related to the underlying cause of the effusion.23,24 Additional clues to the pathogenesis of pulsus paradoxus come from animal and clinical studies which suggest that filling against common RV and LV diastolic pressures that are set by the pericardial pressure– volume relation is necessary for its development, and that absence of pulsus paradoxus in cardiac tamponade associated with LV dysfunction, atrial septal defect, aortic insufficiency, and regional tamponade can be explained by a lack of competitive ventricular filling during inspiration.24–26 It is also important to recognize that pulsus paradoxus (and the clinical and echocardiographic correlates) occur in conditions other than cardiac tamponade, such as constrictive pericarditis, acute and chronic obstructive lung disease, large pleural effusions, RV infarction and pulmonary embolus.26

Because of constrained cardiac filling by the pericardium, progressive qualitative and quantitative changes in systemic venous return develop. Normal venous return is bimodal with peaks during ventricular systole and early diastole. Given that (1) the total cardiac volume is limited by the pericardial effusion, (2) that the volume in a cardiac chamber can increase only when there is an equal decrease in the volume

Fig 3 – (A) LV diastolic pressure–segment length relations before (closed symbols) and after pericardiectomy (open symbols). Dextran infusion shifted the entire curve upward, nitroprusside lower the curve toward control. The same interventions after pericardiectomy did not shift the curve but added higher and lower points along the original curve. (B) Top panel: LV diastolic pressure–segment length relations in response to dextran (closed triangles) followed by nitroprusside infusion (closed squares). Bottom panel: transmural ventricular diastolic pressure replaces cavity pressure, which has the same effect as pericardiectomy. Reproduced with permission from Shabetai.6

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Fig 4 – Schematic diagram of ventricular interdependence. With inspiration there is a shift of the ventricular septum toward the left ventricle that is reversed with expiration. Adapted from Klein et al.4

It cannot be overemphasized that tamponade is a hemodynamic continuum. As pericardial pressures increase, transmural pressures (i.e., cavity minus pericardial pressure) are near zero; thus, distending pressure is reduced. It is this reduction in preload that is responsible for the decreased cardiac output and work in cardiac tamponade and only in agonal cases is myocardial contractility reduced. The reduced LV volume reflects the decreased pulmonary venous return owing largely to compression of the more susceptible RV (series ventricular interdependence).27 Contributing to impaired systolic function is the inspiratory reversal of the transeptal pressure gradient that abolishes the septal contribution to RV systole.28 Interestingly, regional tamponade experiments in canines by Fowler and Gabel29 compared the effects of tamponade of the RV plus both atria to that of the RV alone and tamponade of the LV plus both atria to that of the LV alone. These authors concluded that the hemodynamic effects of tamponade were mainly the result of atrial, not ventricular compression. A subsequent study using the same experimental preparation found that tamponade of both ventricles had a greater hemodynamic effect than tamponade of either ventricle alone, and that tamponade of all four chambers had the greatest hemodynamic effect.30 These findings have important implications for regional tamponade that may occur in the setting of cardiac surgery. Finally, while tamponade has been shown to compress the epicardial coronary arteries, ischemia does not occur as it is balanced by a reduction in preload (and hence, myocardial oxygen demand) and does not contribute to the pathophysiology of cardiac tamponade.6

Pathophysiology of constrictive pericarditis Constrictive pericarditis is a condition in which a thickened, inelastic, scarred, and often calcified pericardium limits diastolic filling and constrains the upper limit of cardiac volume.31 The thickened, rigid pericardium prevents the normal inspiratory decrease in intrathoracic pressure from being transmitted to the heart chambers, causing a dissociation of intracardiac and intrathoracic pressures; as a result,

venous pressure does not decrease, and systemic venous return fails to increase with inspiration. Since the LA and the terminal portions of the pulmonary veins are intrapericardial, pulmonary venous, but not LA pressure declines, and the pulmonary venous-to-LA gradient and flow decrease during inspiration, leading to a reduction in LV volume. Because of ventricular interaction, the right heart volume expands via a shift of the interventricular septum. As in cardiac tamponade, with expiration, the opposite changes occur. With constrictive pericarditis, early diastolic filling is even more rapid than normal. Compression does not occur until the cardiac volume approximates that of the constraining pericardium, which occurs in mid-diastole, at which point filling abruptly stops. Consequently, as constrictive pericarditis becomes more severe, ventricular volumes and stroke volumes are reduced.

Comparison with cardiac tamponade The pathophysiology of constrictive pericarditis readily explains findings on clinical examination, Doppler echocardiography, and cardiac catheterization. While the pathophysiology of constrictive pericarditis shares a number of features with cardiac tamponade, there are important differences (Table 2). Features that are common to cardiac tamponade and constrictive pericarditis include diastolic dysfunction; heightened ventricular interdependence; respiratory variation in ventricular inflow velocities; elevated central venous, pulmonary venous, and ventricular diastolic pressures; and generally, mild pulmonary hypertension. However, the pathophysiology of cardiac tamponade and constrictive pericarditis differs in several respects. First, in cardiac tamponade, the pericardial space is open and transmits the respiratory swings in thoracic pressure to the heart, whereas in constrictive pericarditis, the eliminated pericardial space does not. Second, in cardiac tamponade, systemic venous return increases with inspiration, enlarging the right heart and encroaching on the left, while in constrictive pericarditis, systemic venous return does not increase with normal, resting inspiration; instead, the right to left septal shift is due to the decreased LV diastolic volume. Finally, while in both disorders there is equalization of the RA,

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Table 2 – Pathophysiological differences between cardiac tamponade and pericardial constriction. Cardiac Tamponade

Pericardial Constriction

Pericardial space transmits respiratory swings in thoracic pressure Inspiratory ↑ in venous return Septal shift due to ↑ size of RV Uniform inspiratory ↓ in diastolic pressures ↓ Early diastolic filling (↓Y descent)

Pericardial space does not transmit swings in thoracic pressure No inspiratory ↑ in venous return Septal shift due ↓ size of LV With inspiration, either no change or ↑ of RA pressure and ↓PA wedge pressure ↑ Early diastolic filling (↑Y descent)

RV and LV diastolic, and pulmonary wedge pressures, in cardiac tamponade the elevated pressures decrease in unison with inspiration, whereas in constrictive pericarditis, the RA pressure remains constant during inspiration (or may increase), while the pulmonary wedge pressure decreases.

Comparison with restrictive cardiomyopathy Although there are hemodynamic similarities between constrictive pericarditis and restrictive cardiomyopathy, there are notable pathophysiologic differences. In patients with constrictive pericarditis, total cardiac volume is fixed by the noncompliant pericardium. Because the septum is not involved it can bulge toward the LV when LV volume is less than that on the RV. Thus, ventricular interdependence is greatly enhanced. In addition, in constrictive pericarditis, there is dissociation of intracardiac and intrathoracic pressures. In contrast, pericardial compliance is normal in restrictive cardiomyopathy and intrathoracic pressures are transmitted normally to the cardiac chambers (unless there is coexisting myocardial and pericardial disease as may occur after radiation therapy). Unlike the situation described above for constrictive pericarditis, in restrictive cardiomyopathy, inspiration lowers pulmonary wedge and LV diastolic pressures equally, thereby leaving the pressure gradient for ventricular filling and filling velocity virtually unchanged. A lower LV filling pressure gradient with constrictive pericarditis also leads to a delay in mitral valve opening and therefore, a longer isovolumic relaxation time during inspiration. This inspiratory decline in the filling gradient is seen in constrictive pericarditis but not restrictive cardiomyopathy.

Pathophysiology of effusive-constrictive pericarditis Although the pericardial cavity is typically obliterated in patients with constrictive pericarditis, pericardial effusion may be present in some cases. In this setting, the scarred pericardium not only constricts the cardiac volume but can also increase the pericardial fluid pressure, leading to signs suggestive of cardiac tamponade. Pericardial pathology consistent with constrictive pericarditis with a concomitant effusion is called effusive–constrictive pericarditis.32 Such patients may be mistakenly thought to have only cardiac tamponade; however, elevation of the RA and pulmonary wedge pressures after drainage of the pericardial fluid points to the underlying constrictive process.

Statement of Conflict of Interest The author declares no conflict of interest.

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