Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Pericardial Diseases: Constrictive Pericarditis and Pericardial Effusion
Case Study
A 69-year-old man presented with progressive leg edema, abdominal fullness, shortness of breath, and 30-lb weight gain over the course of 24 months. Past medical history included hypertension and hyperlipidemia on medical therapy. He denied any history of rheumatologic disorder, previous radiation therapy, or cardiothoracic surgery. Physical exam revealed markedly elevated venous pressure ( Video 26.1 ) with prominent x and y descents. Cardiac auscultation showed a high-pitched early diastolic heart sound at the cardiac apex. There was hepatomegaly and bilateral leg edema. Laboratory work revealed normal blood counts, mild elevation in alkaline phosphatase (140 U/L; normal range 40–129), and NT-terminal pro-brain natriuretic peptide (NT-proBNP) (288 pg/mL; reference <97) levels. C-reactive protein level and sedimentation rate were normal. Chest radiography did not show any evidence of pulmonary venous hypertension but revealed calcification of the pericardium. Transthoracic echocardiography (TTE) was performed, showing normal biventricular function and no significant valvular disease. There was severe dilatation of the inferior vena cava (IVC) with minimal inspiratory collapse. Respiratophasic ventricular septal shift ( Video 26.2 ) and expiratory reversals in the hepatic vein pulsed-wave (PW) Doppler were seen. As part of his workup for dyspnea, a chest computerized tomography (CT) was performed; it confirmed the presence of pericardial calcification and revealed marked circumferential thickening of the pericardium ( Fig. 26.1 A). Cardiac magnetic resonance imaging (MRI) confirmed increased pericardial thickening (maximal thickness 9 mm) (see Fig. 26.1 B) without late gadolinium enhancement. The diagnosis of constrictive pericarditis (CP) was made and the patient was referred to surgical pericardiectomy, which was performed without complications.
Epidemiology
CP is a form of diastolic heart failure, secondary to reduced pericardial compliance in the setting of pericardial inflammation and/or fibrosis. The diagnosis of CP in a patient presenting with heart failure is of extreme importance since it is a potentially curable disorder. In addition when left untreated it carries a poor prognosis.
The prevalence of CP is still poorly understood but has been documented in 0.2% to 0.4% of patients following cardiac surgery. Over the past half century, the epidemiology of CP has significantly changed. Although tuberculous pericarditis remains the most common cause of CP worldwide, its occurrence is now extremely rare in the United States and Europe. Concurrently, the number of iatrogenic CP cases (postcardiac surgery and radiation related) has markedly risen. In a series from our institution, idiopathic and postcardiac surgery accounted for more than 65% of CP cases, followed in frequency by radiation. Similar results have also been published by others. Less common causes of CP include connective tissue disorders, malignancy, and trauma.
Pathophysiology
In CP, diastolic filling is limited due to an inelastic or stiff pericardium. Reduced pericardial compliance might be secondary to active inflammation or varying degrees of pericardial fibrosis, scarring, and/or calcification. The development of CP might occur acutely and subacutely, where pericardial inflammation typically prevails, or chronically, in which pericardial fibrosis is the dominant feature. Once felt to be an irreversible condition, it is now well established that a subset of patients with predominantly inflammatory CP can respond to anti-inflammatory therapy, thus foregoing the need for surgical treatment, an entity described as transient CP.
Pericardial thickening is seen in most (80%) but not all patients with CP ( Fig. 26.2 A). Although it is still unclear why a subset of patients will develop pericardial constriction following an insult to the pericardium, it is well established that some etiologies (particularly tuberculous pericarditis) carry a high risk of evolving into a constrictive phase. In contrast, the risk of developing CP after idiopathic or postviral pericarditis has been reported to be low, occurring in less than 1% of individuals.
It should be noted that although CP is primarily a disease of the pericardium, in long-standing, chronic isolated CP cases, myocardial atrophy may also develop. Moreover, CP may occur in patients with preexisting underlying myocardial disease, such as those who received radiation therapy or postcardiac surgery. In these patients, features of CP and restrictive cardiomyopathy (RCM) can then coexist, potentially making the recognition and diagnosis of CP more challenging.
Increased ventricular interdependence and dissociation of intrathoracic and intracardiac pressures are the two hemodynamic hallmarks of CP. The inelastic, scarred pericardium markedly impairs cardiac distention but also prevents variations in intrathoracic pressures to be fully transmitted to the cardiac chambers. As a consequence, during inspiration, the pressure gradient between the pulmonary veins (which are extrapericardial structures) and the left heart decreases, reducing left atrial filling. Thus left ventricular (LV) filling (and consequently LV output) decreases upon inspiration. The ventricular septum then bows leftward, favoring right ventricular (RV) filling as systemic venous return increases. Upon expiration, the opposite occurs: LV inflow increases, RV filling decreases, and the septum shifts rightward. Therefore RV and LV volumes and stroke volumes will inversely vary according to phases of the respiratory cycle—the so-called increased ventricular interdependence or enhanced ventricular interaction. Lastly, the significantly elevated right atrial (RA) and left atrial (LA) pressures promote prominent early diastolic flow into the ventricles; however, pericardial reserve volume is rapidly reached, leading to marked diminution of ventricular filling toward mid-late diastole. This is the origin of the rapid filling on invasive ventricular pressure tracings or increased early diastolic velocity (E)/A ratios by Doppler seen in CP.
Although cardiac tamponade also results in severe abnormalities of diastolic function and elevated filling pressures, it is worth highlighting that its underlying hemodynamics markedly differ from CP. In tamponade, the elevated pericardial pressure impairs diastolic filling (particularly in early diastole). This leads to the hallmark feature of cardiac tamponade on cardiac catheterization: blunting of y descents ( Fig. 26.3 ). Thus, early ventricular diastolic filling in classic cardiac tamponade and CP are actually on opposite ends of a spectrum (blunted vs. enhanced, respectively). Some patients with cardiac tamponade might actually develop constrictive features after pericardiocentesis has been performed and cardiac tamponade has been relieved. This clinical entity has been described as effusive-constrictive pericarditis ; its hemodynamic signature is the persistence of elevated central venous pressures following completed evacuation of the pericardial effusion. The first clue to its diagnosis should be the failure of the jugular venous pressures to normalize following pericardiocentesis, but in these patients features of CP are seen postpericardiocentesis both invasively (cardiac catheterization) and noninvasively (echo Doppler). Clinicians should be aware of the existence of effusive-constrictive pericarditis, as higher rates of pericardiectomy and heart failure hospitalization during follow-up have been described in these patients.
Diagnostic Evaluation
Clinical Presentation and Physical Exam Findings
Individuals with CP will typically present with signs and symptoms of right-sided heart failure, such as elevated venous pressure, ascites, and leg edema. Dyspnea can also be present. CP should always be excluded in patient’s presenting with heart failure with preserved ventricular function and predominant right-sided failure, as well as in those presenting with progressive heart failure in the setting of previous cardiac surgery.
At bedside, elevation in jugular venous pressure is almost universal, with the typical venous contour of CP, showing prominent x and y descents (see Video 26.1 ). This pattern is the opposite of what is typically seen in severe tricuspid regurgitation (TR), where a large positive wave (the V wave) instead of a negative wave (i.e., descent) is present. In CP, an increase in venous pressure upon inspiration might also be seen (Kussmaul sign). This, however, is not pathognomonic of CP and can be seen in any pathology resulting in significantly reduced compliance of the right-sided chambers. Cardiac auscultation can reveal a high-pitched apical early diastolic sound, the so-called pericardial knock; this is a specific but not sensitive finding for the presence of CP. Nonpulsatile hepatomegaly and leg edema are also usually present.
Chest Radiography and Electrocardiography
Pericardial calcification on chest radiography may be seen in patients with CP ( Fig. 26.4 ); however, this finding is only seen in approximately one-fourth of patients with CP. Findings of pulmonary venous congestion, cardiomegaly, or massive biatrial enlargement may be a clue to an underlying cardiomyopathic rather than a pericardial process.
Electrocardiography typically shows nonspecific ST-T wave changes. The presence of large P waves similar to those observed in mitral stenosis has also been reported as an electrocardiographic sign of CP. Lastly, the presence of atrial fibrillation is not an uncommon finding among patients with pericardial constriction.
Laboratory Evaluation
Mild elevation in liver enzymes (especially alkaline phosphatase) and creatinine levels are common in CP. Plasma B-type natriuretic peptide levels have been shown to be lower in patients with CP than in those with RCM. However, there can be significant overlap among those with CP and underlying myocardial disease, such those with radiation-induced CP.
Transthoracic Echocardiography
Currently, TTE is the diagnostic modality of choice for the diagnosis of CP. The echocardiographic diagnosis of constrictive physiology is based on the constellation of two-dimensional (2-D) and Doppler abnormalities that will reflect the hemodynamic pillars of CP: enhanced ventricular interaction, dissociation of intrathoracic-intracardiac pressures, and elevation of ventricular filling pressures. The echo Doppler evaluation should always involve a detailed assessment of septal motion, mitral inflow PW and mitral annular tissue Doppler, medial and lateral tissue Doppler of the mitral annulus, evaluation of IVC size/collapsibility, and PW Doppler of the hepatic veins. It should be highlighted that if CP is suspected, the mimickers of CP should be actively sought and excluded by echocardiography.
Abnormal motion of the ventricular septum is one of the first clues to the echocardiographic diagnosis of CP. One of two abnormalities can be seen: respirophasic septal shift or a septal bounce/shudder. The septal shift is a consequence of the enhanced ventricular interaction and is manifested by respiratory changes in ventricular septal position, with the ventricular septum moving toward the left ventricle during inspiration (as RV volume increases with increased systemic venous return) with opposite motion following expiration ( Fig. 26.5 ; see Video 26.2 ). The detection of respirophasic septal shift is enhanced when longer clips (10 beat) are recorded. Conversely, this finding can be easily missed when short (1-beat or 2-beat) clips are recorded. In our series, respirophasic septal shift was present in 93% of patients with CP, with a positive predictive value of 92% and a negative predictive value of 74%. The septal bounce results from instantaneous pressure differences between diastolic RV and LV pressures. Although a sensitive finding for CP, it has lower specificity, as it might be challenging to distinguish from abnormal septal motion due to conduction abnormalities or postoperative state.
Attention should then be turned to mitral valve/annular Doppler findings. The presence of elevated (≥9 cm/sec) medial e′ in patients presenting with heart failure should be another clue that CP might be present ( Fig. 26.6 ). Early tissue Doppler velocity is a measure of ventricular relaxation and thus medial e′ velocity is expected to be reduced in patients with intrinsic myocardial disorders. In contrast, due to myocardial tethering to the abnormal pericardium, myocardial velocities at the medial mitral annulus tend to be exaggerated in CP. Noteworthy, only a mildly increased medial e′ might be present in patients with CP following cardiac surgery or radiation therapy given the concomitant myocardial disease. In our experience, patients with radiation-induced CP had a lower septal e′ than patients with primary CP (9.5 cm/sec vs 14.5 cm/sec), with patients with postcardiac surgery CP having intermediate values (11.1 cm/sec). Lastly, also a consequence of LV tethering, mitral lateral e′ might be lower than its medial counterpart, which is the opposite of normal (annulus reversus) (see Fig. 26.6 ).
As stated in the diastolic function assessment guidelines, mitral inflow PW Doppler typically shows an E/A ratio above 0.8: An expiratory E/A ratio below 1 makes CP extremely unlikely, as it was seen in only 6% of surgically proven CP cases. Inspiratory reduction in PW mitral early diastolic velocities (E) was one of the first echocardiographic features of CP described (see Fig. 26.6 ), reflecting the underlying dissociation of intrathoracic-intracardiac pressures. Traditionally, inspiratory decreases greater than 25% are suggestive of CP. Although minimal changes in mitral E velocities are present in normal individuals, the degree of respirophasic oscillation in E velocity in patients with CP can be quite variable. Moreover, obesity and primary obstructive pulmonary disorders can also lead to marked variations in mitral E velocities. Thus, although respirophasic variations in mitral E velocities are in keeping with pericardial diseases, its diagnostic yield is limited (a change in mitral E velocity of 15% was found to have a sensitivity of 84% and a specificity of 73% for the diagnosis of CP).
Dilatation of the IVC with abnormal collapsibility is almost a universal finding in CP, and a small-sized IVC should strongly argue against the presence of hemodynamically significant constrictive physiology (an IVC diameter <21 mm or an inspiratory collapse ≥50% was present in only 2% of cases in our CP series). Interrogation of hepatic vein flow by PW Doppler should also be a mandatory step in the echocardiographic evaluation of patients with suspected pericardial disease. The typical feature of CP on hepatic vein Doppler is the presence of enhanced expiratory diastolic flow reversals ( Fig. 26.7 A), with this being the most specific echo Doppler finding for the diagnosis of CP. Hepatic vein Doppler is also extremely helpful in identifying conditions that can mimic CP on echocardiography. In RCM, hepatic vein Doppler will show inspiratory increase in diastolic flow reversals (see Fig. 26.7 B), reflecting the inability of the noncompliant right ventricle to accommodate the inspiratory increase in venous return, whereas hepatic vein Doppler will show systolic flow reversals when severe TR is present (typically holosystolic in very severe cases).
Lastly, the presence of deformation of the cardiac chambers’ contour, tethering of the ventricular walls, or the presence of liver tug (pulling of liver edge by the right ventricle during systole), might provide additional information but should not be used to confirm or refute the diagnosis of CP.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here
