Download Diagnosis and Treatment of Constrictive Pericarditis

Diagnosis and Treatment of Constrictive Pericarditis
Edwin G. Avery, IV, M.D.
Chief, Division of Cardiac Anesthesia
University Hospitals Case Medical Center
Associate Professor of Anesthesiology
Case Western Reserve Univ. School of Medicine
Objectives:
I.
1)
2)
3)
36th SCA Annual Meeting
& Workshops
March 29 – April 2, 2014
New Orleans, LA
Develop a basic understanding of diastolic cardiac function as assessed by cardiac ultrasound exam
Understand the difference between constrictive and restrictive cardiac pathologies
Be aware of the most effective diagnostic modalities employed to determine
the need for pericardiectomy
Pathophysiology of Constrictive Pericarditis
Constrictive pericarditis (CP) represents the final stages in the progression of an inflammatory process resulting from a wide
range of possible pathologies affecting the pericardium (e.g., idiopathic, postsurgical/trauma, infectious, autoimmune disorders,
irradiation, uremia, neoplastic, sarcoid, methysergide therapy). The end result is that the heart’s diastolic function (i.e.
lusitropism) is limited by constriction related to changes in the pericardium (i.e. thickening, fibrosis and calcification), thus the
term constrictive pericarditis. The time course for constriction to occur following an inflammatory insult is variable and may
span from months to years. In some cases the fibrosis with associated thickening can develop rapidly and may be reversible
(most commonly following cardiac surgery).1 The dense fibrosis that characterizes CP commonly involves adhesions between
the visceral and parietal pericardial layers.
From a pathophysiologic standpoint the developed constriction affects lusitropism and effectively limits cardiac chamber
filling. Elevation of systemic and pulmonary venous pressures further characterizes the pathophysiology. In CP the ventricular
chambers are known to fill rapidly in early diastole as a result of the elevated atrial pressures; ventricular filling ceases early
and abruptly when the chamber reaches its limited maximum volumetric capacity. The limited filling capacity of the
ventricle(s) has different pathologic consequences depending on whether one or both sides of the heart are affected. For
example, in an individual with constrictive changes isolated to the right ventricle there will be signs/symptoms of systemic
venous congestion (e.g., hepatic congestion with associated coagulopathy and hepatic dysfunction, peripheral edema, ascites,
anasarca and possibly hepatic cirrhosis). Alternatively, constrictive changes primarily affecting the left ventricle will result in
pulmonary edema/hypertension and respiratory symptoms (e.g., exertional dyspnea, orthopnea and cough) The limited cardiac
filling may also result in a compromised stroke volume and thus reduced cardiac output putting all organs at risk for impaired
perfusion. In individuals suffering from constrictive changes to both sides of the heart the signs and symptoms will be mixed.
Further, the reduced cardiac output may result in physiologic compensatory changes involving the retention of sodium and
water by the kidneys that can contribute to elevation of the already high venous pressures. When CP is severe affected
individuals may develop atrial fibrillation, atrioventricular regurgitation, severe fatique and cachexia.
An important aspect of CP pathophysiology is that the thickened pericardium often insulates the heart from the changes in
intrathoracic pressures that result from normal negative pressure respiration. Under normal physiologic conditions the decrease
in inspiratory pressure during spontaneous respiration results in augmented filling of the right ventricle and some pooling of
blood in the lower compliance pulmonary veins that is associated with decreased filling of the left ventricle. Because the
thickened pericardium effectively insulates the heart from these pressures changes ventricular function is further compromised.
As one might suspect the changes in ventricular filling in this diastolic disorder can result in readily apparent changes in the
movement of the Interventricular septum. In many advanced cases of CP there is a characteristic “septal bounce” observed that
can be seen with a number of diastolic disorders, including restrictive pathologies (e.g., hypertrophic cardiomyopathy, sarcoid
cardiomyopathy, hypertensive cardiomyopathy). To better understand the physiologic changes associated with CP readers are
encouraged to fully review the anatomy and physiology of the pericardium.2,3
II. Diagnosing Constrictive Pericarditis – General Considerations
The accurate diagnosis of CP is complicated by its overlap with the clinical signs and symptoms that characterize other cardiac
pathologies that primarily stem from diastolic dysfunction (e.g., restrictive cardiomyopathies as referenced in the preceding
section). In general while the clinical signs and symptoms may bring the affected patient to seek medical care they are not
specific enough to help make the distinction between constrictive and restrictive physiologic disorders. Thus, other more
advanced diagnostic methodologies are employed that fall into the realm of diagnostic imaging.
The most common diagnostic approach in an individual with apparent signs and symptoms of diastolic dysfunction will include
obtaining a chest roentgenogram, an electrocardiogram and a cardiac ultrasound (i.e. transthoracic and/or transesophageal).
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While the chest film and ECG are of minimal help in making this diagnosis the cardiac ultrasound exam, especially
transesophageal echocardiography is common practice in making the diagnosis of CP. Cardiac ultrasound accomplishes two
essential elements of diagnosing CP; first, to verify the diffuse nature of the presence of pericardial thickening and
calcification, and the second, to demonstrate diastolic dysfunction in the setting of normal to near normal systolic function
and/or normal appearing myocardium. Higher fidelity imaging studies such as cardiac MRI or 320, or 256 slice computed
tomography far outshine transthoracic and even transesophageal echocardiography in quantifying the diffuse nature of the
presence of a thickened pericardium (normally the pericardium is 2-3 mm in thickness). Cardiac MRI, also termed
cardiovascular magnetic resonance (CMR) or cine-based CT imaging may also reveal the characteristic and nonspecific septal
bounce associated with CP and many other forms of diastolic dysfunction. Additionally, CMR is considered the gold standard
for volumetric assessment of the left ventricle and can thus most accurately determine stroke volume and cardiac output (i.e.
systolic function).
Despite the strengths of the higher fidelity, non-ultrasound based imaging modalities, they have historically not been able to
provide the same level of physiologic insight into the collective nature of cardiac physiological dysfunction, somewhat related
to a lack of temporal resolution capacity. However, recent advances in CMR techniques appears to prove that this technique
can also accurately detect and measure the transatrioventricular valvular velocities as well as the transpulmonary venous flow
velocities associated with CP and potentially other cardiac pathologies.4 Further, CMR is also able to provide analysis of both
mitral annular tissue velocities as well as flow propagation velocities across the mitral valve.5
Considering the widespread use, relative accessibility to, relatively shorter time to complete an exam and lower expense
associated with the use of cardiac ultrasound as well as the large body of literature which has accumulated to prove that cardiac
ultrasound examination can accurately and reliably diagnose CP it seems apparent for the present that use of cardiac ultrasound
will remain the mainstay of diagnosis for this disorder. It is anticipated that as the body of literature related to the use of CMR
to diagnose CP grows that it will effectively challenge the use of cardiac ultrasound as the mainstay of diagnosing CP.
III. Diagnosing Constrictive Pericarditis – Cardiac Ultrasound Examination
Pericarditis is an inflammation of the pericardium and can occur as the result of multiple pathologies. Pericarditis may
present as either a chronic or acute process and is often associated with the development of a pericardial effusion. Clinically,
one examines the patient suspected of having pericarditis for the presence of the classic triad of chest pain, ECG evidence of
pericarditis (e.g., diffuse ST segment elevations), and a pericardial rub on auscultation. Etiologies of pericarditis include the
following:




Infections (e.g., postviral, bacterial-especially tuberculosis)
Neoplastic (e.g., primary-mesothelioma or fibrosarcoma; secondary metastatic disease-melanoma, lymphoma, leukemia or direct
extension of a pulmonic or breast tumor)
Immune/Inflammatory (e.g., rheumatoid arthritis, systemic lupus erythematosus, scleroderma, acute rheumatic fever, dermatomyositis,
Wegener’s granulomatosis, mixed collagen vascular disease; post-myocardial infarction (Dressler’s syndrome); uremia; postcardiac
surgery
Intracardiac-pericardial communications (e.g., chest trauma, post-interventional catheter procedures, postmyocardial ventricular
rupture)2.
Echocardiographically, one inspects the pericardium for evidence of thickening that appears as an increase in the brightness, or
echogenicity of the ultrasound signal. Normal pericardial thickness is approximately 2-3 mm. M-mode analysis of a patient
with pericarditis will reveal multiple parallel ultrasound reflections and can be helpful to discern the thickened pericardium
(Figure 1). Multiple echo windows should be obtained to verify the diffuse or localized nature of the pericarditis.
Echocardiography lacks sufficient fidelity to consistently quantify the degree of pericarditis and thus carries an unreliable
sensitivity and specificity for detecting this disorder compared to other imaging techniques (e.g, cardiac MRI or high resolution
(256 or 320 slice) computed tomography).
The evaluation of a subtype of pericarditis termed Constrictive pericarditis is important to be aware of when diagnosing
pericardial disease. Clinically significant constrictive pericarditis (CP) will affect ventricular filling in that it can mimic
restrictive diastolic dysfunction. CP has been reported to occur in 0.2 – 0.3% of cardiac surgical patients and has a number of
pathophysiologic features that include: fibrotic pericardium, inflamed pericardium, calcific thickening of the pericardium,
abnormal diastolic filling, a narrow RV pulse pressure (i.e. the systolic RV pressure is normal but the diastolic RV pressure is
elevated), a prominent early diastolic RV pressure dip and later plateau (termed the “square root sign” (Figure 2)3.
Additionally, the RA pressure exhibits a pronounced systolic drop (y descent followed by an increase and then plateau) that
appears as an “M-like” wave on the CVP tracing (Figure 2).
The diagnosis of CP is made by using a combination of 2D echocardiographic analysis and Doppler analysis. The 2D
echocardiographic exam will generally reveal a thickened, highly reflective pericardium in patients with CP. TEE can detect
the thickened pericardium but computed tomography and magnetic resonance imaging are considered to provide more accurate
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measurements of the pericardial thickness. Table 1 lists a number of nonspecific echocardiographic findings associated with
CP1.
Figure 1. M-mode image (the
arrows highlight a thickened
pericardium).
Avery EG & Shernan SK.
Comprehensive Textbook of
Perioperative Transesophageal
Echocardiography 2ed. Chapter
39. 2010
Figure 2
Table 1. 2D-Echocardiographic Findings Associated with CP
Paradoxical ventricular septal motion
Ventricular septal "bounce"
Diastolic flattening of the posterior LV
Premature mid-diastolic pulmonary valve opening
Spontaneous inspiratory leftward shift of the atrial & ventricular septum
Enlarged hepatic veins
Dilated IVC without variation in size during respiration
Normal ventricular size
Normal or enlarged atria with reduced wall excursion
Doppler assessment of patients with CP is complex in that multiple Doppler modalities are recommended to accurately
diagnose this pathology. Doppler modalities used to assess CP include: pulse wave Doppler transmitral tracings, pulse wave
Doppler pulmonary vein tracings, tissue Doppler imaging of the mitral annulus and color Doppler M-mode (flow propagation,
Vp) of the transmitral inflow. Transmitral blood flow has proven to be a useful diagnostic and prognostic tool for individuals
with CP. By color Doppler assessment patients with CP may exhibit tricuspid or mitral valve incompetence. Similar to
pericardial tamponade, the transmitral pulse wave Doppler profile of most patients with CP will demonstrate an exaggerated
respirophasic variation (i.e. it will decrease by approximately 25% during spontaneous inspiration). Note that up to 20% of
patients with CP will not exhibit this Doppler finding although the application of preload reducing maneuvers (e.g., reverse
Trendelenberg position) may be useful to amplify the transmitral velocity respiratory variation that is expected in these
patients15.
The thickened pericardium insulates the intrapericardial structures from the intrathoracic pressure changes
associated with the respiratory cycle and produces an exaggerated respirophasic variation as a result (as seen in tamponade);
similar respirophasic variation is observed in the pulmonary veins with CP and the S:D ratios observed are similar to those of
patients with restrictive myocardial pathology (e.g., the pulmonary vein diastolic flow velocity will be greater than the systolic
flow velocity in patients with a restrictive LV filling pattern, or S:D ratio < 1)3,18-20. Additionally, unique to CP relative to
restrictive cardiomyopathy is that the peak amplitude of the pulmonary venous D wave has been noted to exhibit pronounced
respiratory variation ( > 18% increase upon inspiration in patients receiving IPPV) in CP20.
During mechanical ventilation the transmitral E-wave velocity will increase with early inspiration in CP, thus the exaggerated
respirophasic variation seen with spontaneously breathing CP patients is also observed with IPPV, although the direction of
change in velocity will be opposite in direction21. The increase in intrathoracic pressure expels blood from the extrapericardial
pulmonary veins into the left atrium which results in an increase in transmitral flow velocity. Again the mechanism for the
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exaggerated respirophasic variation observed in CP patients is that the thickened pericardium insulates the intracardiac
chambers (the LA in this case) from the changes in intrathoracic pressure thus increasing the gradient between the pulmonary
veins and the LA during inspiration. Overall, as with pericardial tamponade, the transmitral velocities will be reduced in
amplitude in CP. Given that the CP limits the volume of both cardiac chambers the inspiratory increase in transmitral E wave
velocity will be accompanied by a simultaneous decrease in transtricuspid E wave velocity for two reasons. First, the increase
in intrathoracic pressure will limit right sided filling and second, the increased filling velocity and increased amount of blood in
the LV will result in a shift of the interventricular septum to the right and thus compromises RV filling during inspiration (i.e.
ventricular interdependence is demonstrated). These changes in the transmitral velocities appear to be reversible with surgical
treatment (pericardial stripping or pericardiectomy) of CP although this therapy has been associated with LV dilation and
transient ventricular diastolic dysfunction 3,20.
Much has been written about making the distinction between CP and restrictive cardiomyopathy (RCM). Both of these
pathologies share the common pathophysiology of decreased left ventricular compliance, but different mechanisms account for
the decreased compliance in each case. In CP the decreased compliance relates to the restrictive nature of the thickened
pericardium while in RCM the restriction is related to pathology within the myocardium (e.g., infiltrative disease of the muscle
or hypertrophy). Recall that severely decreased LV compliance will present a restrictive LV filling pattern (Figure 3)1-3.
Figure 3 – Restrictive Diastology
The differentiation of CP from RCM is best approached by assessing the patient for the described exaggerated respiratory
variation in transmitral Doppler flow velocity profiles and for echocardiographic, or cardiac MRI/high resolution CT scan
evidence of pericardial thickening. As previously discussed above this exaggerated respirophasic variation has been
demonstrated in anesthetized patients using TEE21. Newer echocardiographic modalities that have been used to differentiate
CP from RCM include color M-mode flow propagation velocities (Vp), Doppler tissue imaging (DTI) at the level of the mitral
annulus, and Doppler myocardial velocity gradients (MVGs)23. DTI has been demonstrated to provide a highly sensitive and
specific means to differentiate CP from RCM in one study of a homogeneous CP patient population 24,25. See Table 2. DTI has
been shown to be less sensitive to preload (a limitation of transmitral pulse wave Doppler) in differentiating CP from RCM.
DTI at the level of the lateral mitral annulus provides a reproducible means to align the pulse wave tissue Doppler cursor with
the longitudinal axis of myocardial excursion during relaxation of the muscle. Patients with CP generally have preserved
myocardial diastolic function that therefore will demonstrate normal (Em > 8 cm/sec) myocardial velocities. The converse is
true for patients with RCM in that the muscle is inherently pathologic in these patients with infiltrative cardiomyopathies and
thus will demonstrate abnormal (Em < 8 cm/sec). See Figure 4.
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Figure 4. Transthoracic
TDI of the lateral mitral
annulus in a patient with
CP. Note the high Em
velocity here.
Em
Em
Transthoracic TDI of the
lateral mitral annulus in a
patient with restrictive
physiology. Note the
diminished (Ea) or Em
velocity.
Rajagopalan. Am J Card
2001;87:86-94
Color M-mode, or the velocity of propagation (Vp) of transmitral flow is also recommended to be incorporated into the
assessment of patients suspected of CP. Although the results of color M-mode are not as easily reproduced as DTI it is
advantageous in that it appears to be preload independent and has the benefit of providing both excellent spatial and temporal
resolution of diastolic mitral inflow. Color M-mode assessment of patients with CP will generally demonstrate high values of
flow propagation toward the LV apex while those with RCM will have decreased V p values. See Figure 5.
Figure 5. Transesophageal echocardiographic Color M-mode
(Vp) of a patient with CP. Note the steep slope of the first
aliasing velocity of mitral inflow (140 cm/sec)1.
Transthoracic echocardiographic Color M-mode (Vp) of a
patient with restrictive physiology. Note the much more
gradual slope (35 cm/sec) of the first aliasing velocity as
compared to the tracing displayed above.
The relative sensitivities and specificities of each technique to distinguish CP from RCM are presented in Table 5.
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Table 2. Relative Sensitivity and Specificity of Various Doppler techniques to distinguish CP from RCM.
Sensitivity Specificity
E wave peak (MV)
(resp. variation ≥ 10%)
84
91
D wave peak (Pulmonary Vein)
(resp. variation ≥ 18%)
79
91
Color M-mode
Vp (slope ≥ 100 cm/s)
74
91
Tissue Doppler, (Em ≥ 8 cm/s)
89
100
Note that although these newer Doppler techniques are
considered validated for use in determining diastolic
dysfunction direct validation studies for TEE and patients
receiving IPPV have not been performed.
IV. Treatment of Constrictive Pericarditis
With the less common exception of patients with transient CP (most commonly occurs in patients who have
recently undergone cardiac surgical procedures) the definitive treatment is surgical pericardiectomy. In those
patients who are suspected to have a transient version of the disorder conservative medical treatment and watchful
waiting with the addition of systemic corticosteroids is indicated. Severely ill CP patients with multiple
comorbidities may not tolerate surgical pericardiectomy and thus may not be candidates for the procedure; reported
mortality in one series was 5-15%. Further, radiation induced CP is considered a relative contraindication to
pericardiectomy. The medical management may involve salt restriction, diuretics and avoiding the use of beta
blockers or calcium channels antagonists as affected patients develop tachycardia as this response is a helpful
compensatory mechanism. If atrial fibrillation with a rapid ventricular rate develops in a CP patient then initial
therapy is recommended to be digoxin and only use the beta blockers or calcium channel blockers as a last resort.
Likely because it is unclear as to the exact amount of tissue that must be excised to successfully relieve the
constriction not all patients will improve following pericardiectomy and while not all patients that undergo
pericardiectomy will improve the reported mortality after 7 year follow up was 63% in one single center study.28
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