Differentiating constrictive pericarditis and restrictive cardiomyopathy

INTRODUCTION — Constrictive pericarditis is the result of scarring and consequent loss of the normal elasticity of the pericardial sac. This leads to impairment of ventricular filling in mid and late diastole. As a result, the majority of ventricular filling occurs rapidly in early diastole and the ventricular volume does not increase after the end of the early filling period.

Restrictive cardiomyopathy is characterized by a nondilated rigid ventricle, resulting in severe diastolic dysfunction and restrictive filling that produces hemodynamic changes similar to those in constrictive pericarditis.

Constrictive pericarditis and restrictive cardiomyopathy both lead to diastolic heart failure with normal (or near normal) systolic function, and characteristically abnormal ventricular filling that results in similar clinical and hemodynamic features. However, because of their markedly different treatments, differentiating between the two conditions is critical. In some patients, the correct diagnosis may be readily suggested from the history or routine diagnostic testing. In others, however, this differentiation cannot be diagnosed before biopsy or even surgical exploration.

The distinction between constrictive pericarditis and restrictive cardiomyopathy will be reviewed here. The basic aspects of constrictive pericarditis and idiopathic restrictive cardiomyopathy are discussed separately. (See "Constrictive pericarditis: Diagnostic evaluation" and "Restrictive cardiomyopathies".)

PATHOPHYSIOLOGY OF RESPIRATORY EFFECTS — An understanding of ventricular volume constraints and ventricular interaction is key in any discussion of the hemodynamic differences between constrictive pericarditis and restrictive cardiomyopathy.

In patients with constrictive pericarditis, total cardiac volume is fixed by the noncompliant pericardium. The septum is not involved and can therefore bulge toward the left ventricle (LV) when LV volume is less than that on the right. As a result, ventricular interdependence is greatly enhanced. This bulging may be seen on echocardiography, or in some cases, on cardiac magnetic resonance imaging [1]. In addition, changes in intrathoracic pressure are not transmitted to the cardiac chambers because of obliteration of the pericardial space. (See "Constrictive pericarditis: Diagnostic evaluation".)

In restrictive cardiomyopathy, on the other hand, pericardial compliance is normal. LV systolic function is normal, or in severe cases, may even be reduced. The respiratory variation in intrathoracic pressure is transmitted normally to the cardiac chambers.

The different effects of respiration on ventricular filling between the two diseases may be explained by the following mechanisms:

●In patients with constrictive pericarditis, the pulmonary capillary wedge pressure is influenced by the inspiratory fall in intra-thoracic pressure, while the LV pressure is shielded from respiratory pressure variations by the pericardial scar. Thus, inspiration lowers the pulmonary capillary wedge pressure, and presumably left atrial pressure, but not LV diastolic pressure, thereby decreasing the pressure gradient for ventricular filling. The less favorable filling pressure gradient during inspiration explains the decline in filling velocity. Reciprocal changes occur in the velocity of right ventricular (RV) filling [2,3]. These changes are mediated by the ventricular septum, not by increased systemic venous return.

●In patients with 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 inspiration decline in the filling gradient is seen in constrictive pericarditis but not restrictive cardiomyopathy.

HISTORY AND PHYSICAL EXAMINATION — In the evaluation of a patient with suspected constrictive pericarditis or restrictive cardiomyopathy, the history can provide important clues to other systemic disorders which could predispose to either condition (algorithm 1). In addition, while most patients with constrictive pericarditis and restrictive cardiomyopathy present with symptoms of heart failure, subtle differences in physical findings may suggest a particular diagnosis.

History — In the evaluation of constrictive pericarditis versus restrictive cardiomyopathy, the history is most valuable in identifying a systemic disorder which can predispose to either constrictive pericarditis or restrictive cardiomyopathy:

●A prior history of pericarditis, trauma, cardiac surgery, or a systemic disease that affects the pericardium (eg, tuberculosis, connective tissue disease, malignancy) makes the diagnosis of constrictive pericarditis more likely. (See "Etiology of pericardial disease" and "Constrictive pericarditis: Clinical features and causes", section on 'Constrictive pericarditis'.)

●A history of an infiltrative disease that may involve the heart muscle (eg, amyloidosis, sarcoidosis) favors the diagnosis of restrictive cardiomyopathy. (See "Clinical manifestations and diagnosis of cardiac sarcoidosis" and "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis" and "Restrictive cardiomyopathies", section on 'Clinical features'.)

However, prior thoracic radiation treatment (and rarely amyloidosis) can result in either constrictive pericarditis, restrictive cardiomyopathy, or a condition with features of both constrictive pericarditis and restrictive cardiomyopathy. (See "Cardiotoxicity of radiation therapy for breast cancer and other malignancies" and "Constrictive pericarditis: Diagnostic evaluation".)

Physical examination — The vast majority of patients with both constrictive pericarditis and restrictive cardiomyopathy display elevated jugular venous pressure (JVP) on physical examination (figure 1). From the JVP waveform alone, it is not possible to distinguish between constrictive pericarditis, restrictive cardiomyopathy, tricuspid regurgitation with an enlarged compliant right atrium, or right heart failure (eg, due to RV infarction or pulmonary hypertension). The contour of the jugular venous pulse in all these conditions is dominated by a deep, steep Y descent. (See "Examination of the jugular venous pulse".)

Additional physical examination findings in patients with constrictive pericarditis or restrictive cardiomyopathy can include:

●Kussmaul sign (the lack of an inspiratory decline in JVP)

●Pulsus paradoxus (uncommon)

●Peripheral edema

●Ascites and hepatomegaly

●Pleural effusions

Approximately 50 percent of patients with constrictive pericarditis may present with a pericardial knock (an accentuated heart sound occurring slightly earlier than a third heart sound, which may be audible and rarely is palpable), which is not expected in restrictive cardiomyopathy [4]. Conversely, an audible S3 is frequently present in persons with restrictive cardiomyopathy because of the abrupt cessation of the rapid ventricular filling; this is not usually present in constrictive pericarditis. (See "Restrictive cardiomyopathies", section on 'Clinical features' and "Constrictive pericarditis: Clinical features and causes", section on 'Key signs of constrictive pericarditis'.)

NONINVASIVE TESTING — Patients suspected of having either constrictive pericarditis or restrictive cardiomyopathy, based on history and physical examination, should undergo initial evaluation with electrocardiography (ECG), chest radiography, and echocardiography (algorithm 1). While a particular diagnosis is often made following echocardiography, patients commonly undergo cardiac catheterization, during which invasive hemodynamic evaluation can help elucidate the correct diagnosis [5]. In most patients, particularly those with prior radiation exposure, there is a role for computed tomography (CT) or cardiovascular magnetic resonance (CMR) imaging [5]. Both CT and CMR provide additional detailed anatomic information about adjacent vascular structures and an accurate measurement of pericardial thickness.

Electrocardiogram — The ECG may be helpful in distinguishing constrictive pericarditis from restrictive cardiomyopathy. Depolarization abnormalities (such as bundle branch block), ventricular hypertrophy, pathologic Q waves, or impaired atrioventricular conduction strongly favor restrictive cardiomyopathy. Low voltage and isolated repolarization abnormalities can occur in both conditions, although the latter are more common in constrictive pericarditis. Atrial fibrillation is common in the late stages of both diseases. (See "Constrictive pericarditis: Diagnostic evaluation", section on 'Electrocardiogram' and "Restrictive cardiomyopathies", section on 'Electrocardiogram'.)

Plasma BNP — Plasma concentrations of B-type natriuretic peptide (BNP) are increased in numerous conditions, most notably in patients with LV dysfunction. As a result, plasma BNP has been used in the diagnosis of dyspnea and to assess the efficacy of therapy and estimate prognosis in patients with heart failure. (See "Natriuretic peptide measurement in heart failure".)

BNP is released in response to LV dysfunction and wall stretch. Wall stretch is increased in restrictive cardiomyopathy. However, in constrictive pericarditis, the myocardium is normal, and stretch is limited by the thickened pericardium. These physiologic differences suggest that measurement of plasma BNP might have value in distinguishing between these two disorders.

The usefulness of BNP in differentiating constrictive pericarditis from restrictive cardiomyopathy has been evaluated in several small studies (each with between 11 and 33 patients) [6-8]. Mean BNP levels in patients with restrictive cardiomyopathy have generally been significantly higher than BNP levels seen in patients with constrictive pericarditis (table 1). In addition, many patients with constrictive pericarditis had BNP levels at or below 100 pg/mL, a level generally considered the threshold for a normal BNP value. However, one study reported considerable overlap of the measured BNP levels between patients with constrictive pericarditis and restrictive cardiomyopathy when the BNP value was less than 400 pg/mL [8].

While the data are intriguing, these observations need to be confirmed in a larger number of patients to more thoroughly determine the accuracy of BNP testing for differentiating constrictive pericarditis from restrictive cardiomyopathy. However, because the physiologic rationale is strong, we recommend measurement of plasma BNP early in the evaluation of patients with suspected constrictive pericarditis as a normal value (BNP <100 pg/mL) essentially excludes restrictive cardiomyopathy.

Chest radiography — Calcification of the pericardium strongly suggests constrictive pericarditis, but it can also be seen in other conditions, such as asbestosis, which may or may not be associated with constrictive pericarditis (image 1). However, the absence of calcification is equally compatible with either diagnosis. In one retrospective review of 135 patients with constrictive pericarditis confirmed surgically or at autopsy, only 27 percent had pericardial calcification [9]. The cause of constrictive pericarditis was more likely to be indeterminant when calcification was seen (67 versus 21 percent in the absence of calcification). (See "Constrictive pericarditis: Diagnostic evaluation", section on 'Chest radiograph'.)

Mild cardiomegaly on chest radiography is common in both conditions, but more prominent in restrictive cardiomyopathy. This is generally due to atrial rather than ventricular enlargement. Pulmonary venous congestion with or without pleural effusions can be seen in restrictive cardiomyopathy but would not be expected in constrictive pericarditis. (See "Restrictive cardiomyopathies", section on 'Chest imaging'.)

Pericardial imaging — There is no association between increased pericardial thickness and restrictive cardiomyopathy. However, constrictive pericarditis is usually associated with increased thickness of the pericardium (image 2). A pericardial thickness exceeding 4 mm is highly suggestive of constrictive pericarditis (table 1). However, constrictive pericarditis can also occur in the setting of a nonthickened pericardium. Thus, a normal appearing parietal pericardium does not rule out constrictive pericarditis [10,11]. Pericardial thickness can be evaluated using a variety of imaging techniques, including echocardiography, CT, and CMR imaging. (See "Constrictive pericarditis: Diagnostic evaluation", section on 'Initial tests'.)

While transthoracic echocardiography is the most frequently imaging modality used in the assessment of suspected pericardial disease, it is also one of the least sensitive for detecting pericardial thickening. In a review of 143 patients with surgically confirmed constrictive pericarditis, a pathologically thickened pericardium (>2 mm) was seen in 82 percent [10]. Approximately 40 percent of patients with constrictive pericarditis had pericardial thickening seen on transthoracic echocardiography. In contrast, pericardial thickness on transesophageal imaging correlates strongly with that obtained by CT [12].

In comparison to transthoracic echocardiography, CT and CMR imaging are more sensitive for the detection of increased pericardial thickness. [10,11] In the aforementioned review of 143 patients with surgically confirmed constrictive pericarditis, pericardial thickening was seen by CT imaging in 86 percent of patients (compared to 43 percent with pericardial thickening seen by transthoracic echocardiography) [10]. CMR is similar to CT in its ability to detect pericardial thickening. CMR has a reported accuracy of 93 percent for the ability to detect pericardial thickening of greater than 4 mm [11].

Doppler echocardiography — In addition to its role in evaluating pericardial thickness, transthoracic echocardiography allows for Doppler assessment of hemodynamics, thereby providing significant information that can aid in diagnosing (and differentiating) constrictive pericarditis and restrictive cardiomyopathy. Restrictive cardiomyopathy and constrictive pericarditis share many important hemodynamic characteristics and therefore, have a number of Doppler characteristics in common, most notably a restrictive mitral inflow or ventricular filling pattern (measured as mitral E velocity), with striking E dominance and a short deceleration time (figure 2) [13]. These findings indicate early rapid filling and are seen in both entities.

However, Doppler echocardiography can also provide clues to differentiating constrictive pericarditis and restrictive cardiomyopathy (table 1):

●Respirophasic changes in intrathoracic pressure and ventricular filling – The respiratory variation in ventricular filling velocity in restrictive cardiomyopathy is usually minimal (less than 10 percent), while patients with constrictive pericarditis may have respiratory variations as high as 30 to 40 percent in ventricular filling velocity (similar to that seen in cardiac tamponade). An echocardiographic study of 30 patients (19 with constrictive pericarditis and 11 with restrictive cardiomyopathy) found that significant respiratory variation in the ventricular inflow peak velocity ≥10 percent predicted constrictive pericarditis with a sensitivity and specificity of 84 and 91 percent, respectively [14].

However, the ventricular filling velocity is highly influenced by the level of the left atrial pressure. When left atrial pressure is greatly elevated in a patient with constrictive pericarditis, respiratory variation in ventricular filling may not be observed, whereas patients with lower left atrial pressure (ie, due to volume depletion or earlier stage of disease) may have more noticeable changes in ventricular filling velocities with respiration. Left atrial pressure can be reduced on physical examination by asking a patient to move from the supine to seated position; such a maneuver may elicit the abnormality [15].

The ability to assess respirophasic changes in ventricular filling velocities is challenging in patients with atrial fibrillation, due to the presence of variable cardiac cycle length from beat to beat. While some investigators have suggested that respiratory variation can be accurately assessed in patients with atrial fibrillation, we find this to be quite challenging in the average patient [16].

Respiratory variation in mitral E velocity, as with pulsus paradoxus on physical examination, is not specific to constrictive pericarditis and is frequently seen in patients with chronic obstructive pulmonary disease (COPD). In an attempt to distinguish between constrictive pericarditis and COPD, the pulsed-wave Doppler recordings of mitral and superior vena cava flow velocities were compared in 20 patients with COPD who had a 25 percent respiratory variation in mitral E-wave velocity and 20 patients with surgically proven constrictive pericarditis [17]. The patients with pulmonary disease had a marked increase in inspiratory superior vena cava systolic flow velocity which was not seen in those with constrictive pericarditis (waveform 1).

●Hepatic venous flow – Measurement of hepatic venous flow can help to distinguish constrictive pericarditis from restrictive cardiomyopathy. In patients with constrictive pericarditis, there is a reversal of forward flow during expiration, since the RV becomes less compliant as the LV fills more. In contrast, reversal of hepatic vein flow occurs during inspiration in restrictive cardiomyopathy.

●Pulmonary regurgitant flow velocity – Reflecting the characteristic diastolic RV pressure pattern in constrictive pericarditis, velocities at the early diastolic peak, mid-diastolic inflection point, and late diastolic minimal point of the continuous-wave Doppler waveform of pulmonary regurgitation were lower in patients with constrictive pericarditis (n = 15) than in patients with restrictive cardiomyopathy (n = 18) and normal subjects (n = 20) [18].

●Color M-mode flow propagation – Early diastolic color M-mode Doppler shows an excessively rapid transit of blood flow from the mitral orifice to the apex in constrictive pericarditis, whereas the transit is much slower than normal in restrictive cardiomyopathy.

Tissue Doppler imaging — Tissue Doppler imaging provides additional information on myocardial function which can help to distinguish constrictive pericarditis from restrictive cardiomyopathy (table 1). In addition, information derived from tissue Doppler imaging can be used in conjunction with information derived from traditional Doppler imaging to aid in making a diagnosis.

●Doppler tissue velocity – The early diastolic Doppler tissue velocity at the mitral annulus (E') is decreased (<8 cm/s) in restrictive cardiomyopathy, due to an intrinsic decrease in myocardial contraction and relaxation. In contrast, the transmitral E' is frequently increased (>12 cm/s) in constrictive pericarditis, since the longitudinal movement of the myocardium is enhanced because of constricted radial motion (waveform 2) [14,15,19].

While E' values <8 cm/s or >12 cm/s are highly specific for restrictive cardiomyopathy or constrictive pericarditis, respectively, many patients will have an E' velocity between 8 cm/s and 12 cm/s, which is nondiagnostic. Despite excellent specificity of E' for differentiating restrictive cardiomyopathy from constrictive pericarditis, its sensitivity is more modest.

Unlike in normal individuals, mitral lateral (and tricuspid) annular E' velocities are often relatively reduced in patients with constrictive pericarditis ("annular reversus"). This reduction may be the result of lateral adhesion of the pericardium while the longitudinal movement of the septal annulus is unimpeded. These mechanics are not evident in restrictive cardiomyopathy. Thus, the ratio between lateral (both mitral and tricuspid) and septal annuli velocities is reduced in patients with constrictive pericarditis compared with that in patients with restrictive cardiomyopathy (and controls) and may be useful to discriminate these groups of patients. In a study of 37 patients with constrictive pericarditis, 35 patients with restrictive cardiomyopathy (the majority with amyloidosis) and 70 normal controls, the lateral E'/septal E' ratios were 0.94±0.17, 1.35±0.31, and 1.36±0.24, respectively [20].

Of note, in a study of 130 patients with surgically confirmed constrictive pericarditis, the variables independently associated with constriction were ventricular septal shift, medial mitral e', and hepatic vein expiratory diastolic reversal ratio. When septal shift was present with either medial e' ≥9 cm/s or a hepatic vein expiratory diastolic reversal ratio ≥0.79, the sensitivity and specificity for constriction were 87 and 91 percent, respectively [21]. Similar findings were reported among 107 patients with surgically confirmed constrictive pericarditis from a different high-volume center, where the combination of septal shift with medial e' ≥9 cm/s was associated with high sensitivity (80 percent) and specificity (92 percent) for the correct diagnosis [22].

●Strain analysis – Using tissue Doppler to assess myocardial strain may be helpful in distinguishing between constrictive pericarditis and restrictive cardiomyopathy. In a cohort of 92 patients (28 with constrictive pericarditis, 30 with restrictive cardiomyopathy, and 34 controls) who were imaged with both echocardiography and CMR, echocardiographically-derived measures of global longitudinal strain were significantly lower in patients with restrictive cardiomyopathy compared with patients with constrictive pericarditis or controls (with no significant difference seen between constrictive pericarditis and controls) [19]. There was a nonsignificant trend toward reduced measures of circumferential strain in patients with restrictive cardiomyopathy. The addition of global longitudinal strain to respiratory septal shift and early diastolic mitral annular velocity improved the ability to distinguish constrictive pericarditis from restrictive cardiomyopathy.

●Myocardial velocity gradient – Pulsed-wave tissue Doppler imaging may help to distinguish between constrictive pericarditis and restrictive cardiomyopathy by measuring the myocardial velocity gradient, which is an index of myocardial contraction and relaxation that quantifies the spatial distribution of intramural velocities across the myocardium (waveform 2). One study evaluated this use for pulsed-wave tissue Doppler imaging in 15 patients with restrictive cardiomyopathy, 10 patients with constrictive pericarditis, and 30 age-matched normal controls [23]. The Doppler myocardial velocity gradient, as measured from the LV posterior wall in early diastole and during ventricular ejection, was significantly lower in patients with a restrictive cardiomyopathy compared to those with constrictive pericarditis and to normal controls.

●Other tissue Doppler parameters – In a study of 17 patients with constrictive pericarditis, 12 patients with restrictive cardiomyopathy, and 15 controls, measurement of systolic mitral annular velocity (S') and the time difference between the onset of transmitral flow and the onset of E' (T(E'-E)) was shown to increase sensitivity and provide incremental diagnostic discriminating information to E' [24].

Speckle tracking echocardiography (STE) — Regional longitudinal strains measured with STE may avoid the limitations of tissue Doppler annular velocities when patients have a calcified annulus.

The ratios of LV free wall systolic strain/septal wall systolic strain and RV free wall strain/septal strain were significantly lower in 52 patients with constrictive pericarditis (0.8±0.2, 0.8±0.4) than in 35 patients with restrictive cardiomyopathy (1.1±0.2, 1.4±0.5) and 26 control subjects (1.0±0.2, 1.2±0.2). The strain ratios were more robust than the ratio of annular tissue velocities. In patients with constrictive pericarditis, the regional myocardial mechanics significantly correlated with regional pericardial thickness and improved after pericardiectomy [25].

In constrictive pericarditis, global longitudinal strain is generally preserved (although tethering of the pericardium may result in reduced lateral wall but preserved septal longitudinal strain), whereas circumferential strain and torsion are reduced [26].

Cardiovascular magnetic resonance (CMR) — In addition to the ability to detect pericardial thickness and pericardial inflammation, CMR may help differentiate constrictive pericarditis from restrictive cardiomyopathy (table 1).

●Relative atrial volume ratio, the ratio between left (LA) and right atrial (RA) volume, was significantly greater in 23 patients with constrictive pericarditis than in 22 patients with restrictive cardiomyopathy (1.5±0.29 versus 1.12±0.33). A partition value of 1.32 for the relative atrial ratio yielded a sensitivity of 82.6 percent and specificity of 86.4 percent for the diagnosis of constrictive pericarditis [27].

●In the above study of 45 patients with either constrictive pericarditis or restrictive cardiomyopathy, late gadolinium enhancement (LGE) was present in 31.8 percent of patients with restrictive cardiomyopathy and absent in all patients with constrictive pericarditis and normal subjects [27]. In another study, patients with biopsy-proven cardiac amyloidosis had a pattern of LGE involving the entire subendocardial circumference; the positive and negative predictive values for diagnosing cardiac amyloidosis were 92 and 85 percent, respectively [28].

●In a cohort of 92 patients (28 with constrictive pericarditis, 30 with restrictive cardiomyopathy, and 34 controls), both STE- and CMR-derived measures of global longitudinal strain using tissue tracking were significantly higher in patients with constrictive pericarditis than restrictive cardiomyopathy; diagnostic discrimination was comparable with echo and CMR [19]. (See 'Tissue Doppler imaging' above.)

●Real-time cine MRI-ventricular septal position and shape during early ventricular filling could distinguish constrictive (n = 18) and inflammatory pericarditis (n = 6) from restrictive cardiomyopathy (n = 15) and normal subjects (n = 17). The degree of ventricular coupling, as measured as the difference in the maximal septal excursion between inspiration and expiration, was significantly greater in patients with constrictive pericarditis (20±4.5 percent) and inflammatory pericarditis (14.8±3.2 percent) than in normal subjects (7.0±2.4 percent) and patients with restrictive cardiomyopathy (4.2±1.7 percent). A partition value of 11.8 percent completely differentiated constrictive pericarditis from restrictive cardiomyopathy [1].

CARDIAC CATHETERIZATION — In some cases, particularly when there are multiple potential etiologies for heart failure, invasive cardiac catheterization is required to determine the diagnosis. Elevation and equalization of diastolic filling pressures occurs in patients with constrictive pericarditis. Although these hemodynamic findings may occur in patients with other cardiac disorders, their presence is required for the diagnosis of constrictive pericarditis. Diastolic equalization may not be present in patients with constrictive pericarditis in the event of preceding diuresis and a low volume state, as well as in patients with relatively early stage disease. In patients with a low volume state, however, the cardiac output will be low. Therefore, the presence of normal cardiac output with normal filling pressures precludes the presence of hemodynamically significant constrictive pericarditis.

●End-diastolic pressures – RV and LV end-diastolic pressures (RVEDP and LVEDP) are equal or nearly equal in constrictive pericarditis, while LVEDP is usually higher than RVEDP in restrictive cardiomyopathy. However, in many cases of restrictive cardiomyopathy the plateau of diastolic pressure is equally elevated in both ventricles, as typically occurs in constrictive pericarditis. If the pressures are approximately equal, a fluid bolus, exercise, or pharmacologic maneuver should theoretically increase LVEDP above RVEDP in restrictive cardiomyopathy, but the data supporting this theory are not convincing [29-31]. The sensitivity and specificity of such maneuvers are not known; therefore, the diagnostic benefit of these maneuvers is uncertain.

●Dip and plateau sign – The first observations of the dip and plateau configuration (figure 3) of ventricular pressure (also called the square root sign) during diastole led investigators to theorize that ventricular filling during early diastole must be unusually rapid and aided by augmented suction, and that ventricular filling must be halted by pericardial restraint from the end of the first third of diastole onward [32]. This conjecture was verified after it became possible to record the pattern of ventricular filling by ventriculography and subsequently by other imaging techniques. Although some disagree, most authors believe (as we do) that the same dip and plateau waveform seen in constrictive pericarditis also characterizes restrictive cardiomyopathy [33,34].

●Equalization of pressures – Equalization of filling pressures in the four cardiac chambers is commonly said to be a major hemodynamic criterion for the diagnosis of constrictive pericarditis. This statement may be an oversimplification for two reasons:

•The pulmonary wedge pressure falls during inspiration while systemic venous pressure remains constant. Thus, it is not reasonable to expect the two pressures to be precisely equal throughout the respiratory cycle, and frequently equilibration is present only during inspiration.

•Equilibration of diastolic pressures occurs in some patients who have heart failure or an acute volume overload, but who do not have constrictive pericarditis.

In addition, pericardial restraint from a dilated heart may cause equilibration of diastolic pressures and may simulate the hemodynamics of constrictive pericarditis. Examples of this phenomenon are found in RV dilation after RV infarction or severe tricuspid insufficiency, as well as in acute mitral regurgitation secondary to rupture of a chorda tendineae.

Pulmonary hypertension and LV diastolic pressure that exceeds that in the RV by ≥5 mmHg may favor a diagnosis of cardiomyopathy (restrictive or dilated) rather than constrictive pericarditis. However, neither of these findings is highly specific for either diagnosis [35,36].

Hemodynamic maneuvers, such as exercise, fluid loading, and observing postextrasystolic beats, have been proposed as a way to cause diastolic pressures (equal in the two ventricles) to differ. Published experience with these approaches is limited. In addition, there may not be equalization of diastolic pressures if a patient with constrictive pericarditis has been on diuretics and has low to normal right atrial pressures. In such patients, fluid loading at the time of catheterization is necessary to attempt to confirm the diagnosis of constrictive pericarditis.

●Respiratory changes – As noted above, both constrictive pericarditis and restrictive cardiomyopathy may have similar findings of early rapid diastolic filling and elevation and equalization of diastolic pressures in all four cardiac chambers. However, the respiratory changes in filling of the LV and RV, as well as the enhanced ventricular interaction seen in constrictive pericarditis, result in distinctive changes in the LV and RV pressures during respiration (table 1). Mirror image discordance, measured as the inspiratory increase in the ratio of areas under the RV and LV systolic pressure curves (systolic area index), was 97 and 100 percent accurate, respectively, for differentiating 59 cases of surgically proven constrictive pericarditis from 41 cases of restrictive cardiomyopathy [37]. (See 'Pathophysiology of respiratory effects' above.)

These abnormalities have been described as discordance between the pressures in these two chambers, typically seen as reciprocal changes in stroke volume, pulse pressure, or peak systolic pressure during respiration (figure 4):

•During inspiration, there is less filling of the LV, resulting in a large fall in LV systolic pressure. The reduction in LV filling is due to the fall in the pulmonary wedge pressure and presumably left atrial pressure resulting from the decrease in intrathoracic pressure. In contrast, left ventricular diastolic pressure does not fall since the LV pressure is shielded from respiratory pressure variations by the pericardial scar. The net effect is a reduction in the pressure gradient for ventricular filling.

•Due to enhanced ventricular interaction, since the septum can move normally, there is greater filling of the RV and the RV systolic pressure will rise.

These findings are not present in patients with restrictive cardiomyopathy in whom the LV and RV pressures are concordant during the respiratory cycle. Inspiration lowers pulmonary wedge and LV diastolic pressures equally, thereby leaving the pressure gradient for ventricular filling and filling velocity virtually unchanged. (See "Constrictive pericarditis: Diagnostic evaluation", section on 'Differential diagnosis'.)

●A simplified method to detect enhanced ventricular interaction in the catheterization laboratory using aortic and pulmonic ejection times (ie, surrogates for stroke volumes) has been described [38]. Ventricular interaction was assessed by evaluating the difference of aortic and pulmonary artery ejection times from expiration to inspiration. The difference was significant in a 10-patient cohort with surgically proven constrictive pericarditis versus 10 patients with restrictive cardiomyopathy or severe tricuspid regurgitation (50.8±22.5 ms versus 5.4±15.2 ms). Although the method is potentially useful, discordant ejection times are not specific for constriction and further validation is needed.

●Ratio of right atrial pressure (RAP) and pulmonary artery wedge pressure (PAWP) – RAP fairly closely approximates pericardial pressure, while PAWP approximates LVEDP (in the absence of mitral stenosis). It has been hypothesized that a larger contribution of pericardial restraint, as shown by a greater RAP/PAWP ratio (table 1), could help identify patients with "pure" constriction (ie, minimal contribution of myocardial disease to symptoms) in whom pericardiectomy is more likely to be beneficial. In a single-center retrospective study of 113 patients with surgically confirmed constrictive pericarditis, those with values above the median (mean RAP/PAWP ratio 0.86) had greater pericardial thickness (6.6 versus 4.5 mm) and greater postoperative survival [3,5]. This approach is similar to examining for diastolic equalization of intracardiac pressures. While potentially useful, the RAP/PCWP ratio should not be used in isolation and requires further validation.

●Biopsy – Endomyocardial or, less commonly, pericardial biopsy may be helpful when hemodynamic and imaging studies fail to establish the diagnosis [39,40].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pericardial disease".)

SUMMARY AND RECOMMENDATIONS — Patients with both constrictive pericarditis and restrictive cardiomyopathy have elevated left and right sided filling pressures, often of equal magnitude, and usually have normal systolic ventricular function. Findings that can aid in distinguishing the two conditions include (table 1):

●History – The history may provide helpful clues, such as prior pericarditis or a systemic disease predisposing to constrictive pericarditis, or a cause of restrictive cardiomyopathy (eg, diabetes mellitus or amyloidosis). (See 'History' above.)

●Physical Examination – The vast majority of patients with both constrictive pericarditis and restrictive cardiomyopathy display elevated jugular venous pressure (JVP), making this physical finding less helpful in distinguishing the two conditions. The presence of a pericardial knock (an accentuated heart sound occurring slightly earlier than a third heart sound) favors constrictive pericarditis, while an audible S3 is frequently present in persons with restrictive cardiomyopathy. (See 'Physical examination' above.)

●Electrocardiography – The ECG may be helpful in distinguishing constrictive pericarditis from restrictive cardiomyopathy. Depolarization abnormalities (such as bundle branch block), ventricular hypertrophy, pathologic Q waves, or impaired atrioventricular conduction strongly favor restrictive cardiomyopathy. (See 'Electrocardiogram' above.)

●B-type natriuretic peptide (BNP) – We recommend measurement of plasma BNP early in the evaluation of patients with suspected constrictive pericarditis, as a normal value (BNP <100 pg/mL) essentially excludes restrictive cardiomyopathy (table 1). (See 'Plasma BNP' above.)

●Chest radiography – Calcification of the pericardium (except for scattered calcified plaques which are more consistent with prior asbestos exposure) strongly suggests constrictive pericarditis (image 1), whereas cardiomegaly on chest radiography (generally due to atrial rather than ventricular enlargement) is more prominent in restrictive cardiomyopathy. (See 'Chest radiography' above.)

●Pericardial imaging – Increased thickness or calcification of the pericardium favors the diagnosis of constrictive pericarditis, although increased pericardial thickness is not present in all patients. Thickening of the ventricular wall and septum, abnormal myocardial texture, and to a lesser extent, mitral or tricuspid regurgitation favor the diagnosis of restrictive cardiomyopathy. (See 'Pericardial imaging' above.)

•Doppler echocardiography – Doppler echocardiography can provide clues to differentiating constrictive pericarditis and restrictive cardiomyopathy (table 1). (See 'Doppler echocardiography' above.)

-The respiratory variation in ventricular filling velocity in restrictive cardiomyopathy is usually minimal (less than 10 percent), while patients with constrictive pericarditis may have respiratory variations as high as 30 to 40 percent in ventricular filling velocity.

-Hepatic venous flow reversal is expiratory in constrictive pericarditis, but inspiratory in restrictive cardiomyopathy.

-Diastolic mitral regurgitation suggests restrictive cardiomyopathy.

●Tissue Doppler imaging – Tissue Doppler imaging provides additional information on myocardial function which can help to distinguish constrictive pericarditis from restrictive cardiomyopathy (table 1). (See 'Tissue Doppler imaging' above.)

•The early diastolic Doppler tissue velocity at the mitral annulus (E') is decreased (<8 cm/s) in restrictive cardiomyopathy, due to an intrinsic decrease in myocardial contraction and relaxation. In contrast, the transmitral E' is frequently increased (>12 cm/s) in constrictive pericarditis, since the longitudinal movement of the myocardium is enhanced because of constricted radial motion (waveform 2). While E' values <8 cm/s or >12 cm/s are highly specific for restrictive cardiomyopathy or constrictive pericarditis, respectively, many patients will have an E’ velocity between 8 cm/s and 12 cm/s, which is nondiagnostic.

•The Doppler myocardial velocity gradient, as measured from the left ventricular (LV) posterior wall in early diastole and during ventricular ejection, was significantly lower in patients with a restrictive cardiomyopathy compared to those with constrictive pericarditis and to normal controls.

●Cardiac catheterization – Right ventricular (RV) and LV end-diastolic pressures (RVEDP and LVEDP) are equal or very nearly equal in constrictive pericarditis, while LVEDP is usually higher than RVEDP in restrictive cardiomyopathy. However, in many cases of restrictive cardiomyopathy the plateau of diastolic pressure is equally elevated in both ventricles as typically occurs in constrictive pericarditis.

If the pressures are approximately equal, a fluid bolus, exercise, or pharmacologic maneuver should theoretically increase LVEDP above RVEDP in restrictive cardiomyopathy. Mirror-image discordance between RV and peak LV systolic pressures during inspiration is another sign of increased ventricular interdependence (table 1); during peak inspiration, an increase in RV pressure occurs when LV pressure is lowest [35] (See 'Cardiac catheterization' above.)

●Biopsy – Endomyocardial, or less commonly, pericardial biopsy may be helpful when hemodynamic and imaging studies fail to establish the diagnosis. (See 'Cardiac catheterization' above.)