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A 35-year-old woman with a past history of Hodgkin lymphoma was referred for a second opinion for symptoms of progressive dyspnea and lightheadedness on exertion. An understanding of cardiac physiology and pathophysiology allowed us to explain her symptoms and signs and make the diagnosis.
A 35-year-old woman with a past medical history of Hodgkin lymphoma treated in 2002 with chemotherapy and radiation to the neck and mediastinum was referred for worsening dyspnea and lightheadedness on exertion. She denied chest pain, syncope, cough, sputum, orthopnea, and paroxysmal nocturnal dyspnea. Physical examination was remarkable for resting tachycardia, a blood pressure of 99/64 mm Hg, increased jugular venous pressure (JVP) during inspiration, a third heart sound, and pedal edema. The lungs were clear to auscultation.
The patient had had extensive testing before referral. Spirometry, lung volumes, and diffusing capacity were normal. Chest computed tomography scan was normal except for mild postradiation changes adjacent to the right hilum. Transthoracic echocardiography showed normal LV function with no valvular abnormalities. The right ventricle was normal in size and contractility. There was no evidence of pulmonary hypertension. A cardiopulmonary exercise test was stopped early due to lightheadedness. At peak exercise, there was a reduction in blood pressure and a reduced oxygen pulse suggesting an inability to augment stroke volume.
At our institution, the patient underwent a left and right heart catheterization. Hemodynamic findings were recorded before and after infusing 1 L of normal saline (Table 1). Representative examples of the right ventricular (RV), left ventricular (LV), and pulmonary capillary wedge pressure tracings are shown in Figures 1 and 2. Cardiac magnetic resonance imaging (MRI) showed “septal bounce” and mild pericardial enhancement without definite thickening.
| Chambers | Mean RA | RVEDP | PA | PCWP | LVEDP | LV (Systolic/Diastolic) | CO/CI (Fick) |
|---|---|---|---|---|---|---|---|
| Baseline | 16 | 16 | 23/13 | 13 | 10 | 110/10 | 8.05/4.65 |
| Fluid load | 17 | 18 | 25/18 | 20 | 19 | 115/19 | 8.00/4.61 |
Figure 1. Pressure tracing from the left ventricle (LV) and right ventricle (RV). During inspiration (INSP), there is a decrease in the LV systolic pressure and a concomitant increase in the RV systolic pressure. EXP = expiration.
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Figure 2. Pressure tracing from the left ventricle (LV) and pulmonary capillary wedge pressure (PCWP). The PCWP varies with the respiratory cycle, while the LV diastolic pressure remains constant. EXP = expiration; INSP = inspiration.
[More] [Minimize]1. What findings on physical examination, cardiopulmonary exercise test, MRI, and cardiac catheterization were helpful in making the correct diagnosis?
2. How can these findings be explained by the underlying pathophysiology?
The increased JVP during inspiration suggested inability of the right ventricle to accommodate the increased venous return that occurs during inspiration, and the third heart sound was consistent with a “pericardial knock.” The reduced oxygen pulse and blood pressure at peak exercise suggested inability to augment cardiac output. These findings, together with the history of mediastinal irradiation, raised the possibility of constrictive pericarditis. Cardiac catheterization was diagnostic by demonstrating near equalization of RV and LV end-diastolic pressures and dissociation of RV and LV systolic pressure changes during the respiratory cycle. As shown by our patient, these characteristic findings may be evident only after hypovolemia has been corrected with a rapid volume challenge. As in this case, MRI shows normal pericardial thickness in up to 20% of patients with surgically confirmed constrictive pericarditis.
The definitive treatment for constrictive pericarditis is surgical pericardiectomy. Although there are no randomized trials comparing medical management with surgery, observational studies suggest that a nonsurgical approach usually leads to progressive heart failure and death. On the other hand, surgery is accompanied by significant perioperative mortality that ranges from 2.7% in patients with idiopathic pericarditis to as much as 21.4% in those with postradiation constriction. The decision to go to surgery must, therefore, be highly individualized and involve a frank discussion between the patient and a multispecialty physician team. Although we recommended pericardiectomy, our patient decided against surgery given the high perioperative mortality. She is still alive 1 year later.
The pericardium is a bilayer sac made of a thin inner and thicker fibrous outer layer that contains a potential space called the pericardial cavity. The pressure in the pericardial cavity is slightly subatmospheric (−3 to −6 mm Hg) under normal physiologic conditions. Pericardial pressure is equal to and tracks with pleural pressure. Thus, under normal conditions, the pericardial transmural (distending) pressure is close to zero.
Although it encloses the heart, the normal pericardium is distensible and does not limit diastolic ventricular filling. It also allows respiratory variations in pleural (intrathoracic) pressure to be transmitted to the cardiac chambers. Because pleural pressure is also transmitted to the superior vena cava and the pulmonary veins, the pressure gradient driving right and left atrial and ventricular filling normally does not vary during the respiratory cycle.
Inflammation and fibrosis of the pericardial sac reduce its compliance and distensibility. When sufficiently severe, the stiff pericardium limits myocardial expansion and ventricular filling, which leads to symptoms and signs of biventricular diastolic heart failure. The most common causes of constrictive pericarditis are cardiac surgery, cardiac radiation, and connective tissue diseases, although in many cases, the underlying etiology remains undetermined. The diagnosis of constrictive pericarditis requires an understanding of three characteristic pathophysiologic features, which can be identified by physical examination, echocardiography, MRI, and cardiac catheterization (Table 2).
| Pathophysiologic Features | Impaired Ventricular Filling | Pathologic Ventricular Interdependence and Dissociation of Intrathoracic and Intracardiac Pressures |
|---|---|---|
| Examination | Kussmaul’s sign | Pulsus paradoxus |
| Pericardial knock | ||
| Echocardiogram | Rapid early diastolic flow | Respiratory variation in septal movement, mitral and tricuspid valves inflow |
| MRI | N/A | Respiratory variation in septal movement |
| Pericardial thickening | ||
| Catheterization | Diastolic atrial and ventricular dip and plateau | Respiratory discordance of systolic pressures |
| Elevated atrial pressures with M pattern | ||
| Elevation and equalization of diastolic pressures |
Ventricular filling is unimpeded during early diastole, and elevated atrial pressure causes rapid flow across the mitral and tricuspid valves. As ventricular volume reaches the limit imposed by the stiff pericardium, however, filling abruptly stops. This rapid drop in blood flow may be detected as a third heart sound, which is referred to as a pericardial knock. Intraventricular pressure tracings reflect this as a dip and plateau or square root pattern (Figure 3). Ventricular relaxation followed by rapid inflow causes a drop (the dip) and then a rapid increase in ventricular pressure. Once the ventricles have expanded to meet the constricting pericardial shell, flow stops and ventricular pressure remains constant (the plateau).
Figure 3. Simultaneous right ventricle (RV) and left ventricle (LV) pressure recordings demonstrating equalization of pressures in diastole as well as the characteristic dip and plateau pattern.
[More] [Minimize]During spontaneous inspiration, the drop in pleural pressure increases blood flow into the right atrium, which normally decreases JVP. In patients with constrictive pericarditis, the inelastic pericardium prevents the right ventricle from accommodating the increased venous return, and this causes a paradoxical elevation in JVP that is referred to as Kussmaul’s sign (Figure 4).
Figure 4. Right atrial (RA) tracings from a patient with constrictive pericarditis. Note that the mean RA pressure rises during inspiration (INSP) (Kussmaul’s sign). EXP = expiration.
[More] [Minimize]Jugular venous and atrial pressure waveforms typically have a characteristic “M” pattern that is produced by large a and v waves with deep and rapid x and y descents (Figure 5). The prominent a wave occurs when the atrium contracts against a noncompliant ventricle at end-diastole. The deep x descent is due to atrial relaxation and movement of the atrioventricular valves toward the outflow tracts during ventricular systole. The elevated v wave reflects high diastolic filling pressures. Finally, the deep y descent is caused by initial resistance-free diastolic ventricular filling and is followed by a rapid increase to a constant pressure. This corresponds to the dip and plateau in intraventricular pressure.
Figure 5. Simultaneous right atrial (RA) and left ventricle (LV) tracings showing diastolic equalization and M-shaped pattern of RA tracing with prominent x and y descents.
[More] [Minimize]By encasing the heart, the rigid pericardium limits total ventricular volume. This means that an increase in the volume of one ventricle must cause a decrease in the volume of the other. This abnormal coupling of right and left ventricular volumes is referred to as pathologic ventricular interdependence.
In patients with constrictive pericarditis, the thick pericardium prevents much of the ventilation-induced change in pleural pressure from being transmitted to the cardiac chambers, but it has no effect on the respiratory pressure variation within the superior vena cava and pulmonary veins. This uncoupling of intrathoracic and intracardiac pressures changes the gradient driving blood into the atria and ventricles and is a key diagnostic feature of constrictive pericarditis (Figure 6).
Figure 6. Respiratory variation in transvalvular flow velocities in constrictive pericarditis. With inspiration, the pressure gradient from the pulmonary veins to the left heart decreases, resulting in decreased mitral inflow. Decreased left ventricular (LV) volume causes leftward septal shift. Given the fixed cardiac volume, this leads to increased flow through the tricuspid valve. During expiration, mitral inflow increases and tricuspid inflow falls. LA = left atrium; RA = right atrium; RV = right ventricle.
[More] [Minimize]During spontaneous inspiration, pulmonary venous pressure falls more than left atrial pressure, thereby reducing LV filling. Although the pressure gradient driving right-sided filling also falls, the increase in venous return and the decrease in LV size (pathologic ventricular interdependence) causes an increase in RV volume and a leftward shift of the interventricular septum. During expiration, the pulmonary venous–left atrial gradient increases, and venous return to the right heart falls. This increases LV volume at the expense of the RV and shifts the interventricular septum back to the right.
The combination of pathologic ventricular interdependence and dissociation of intrathoracic and intracardiac pressures can be demonstrated in a number of ways. Pulsus paradoxus may be present on physical examination. Ventilation-induced septal movement and variation in ventricular size can be detected by echocardiography and MRI. Doppler echocardiography can be used to demonstrate respiratory variation in tricuspid and mitral inflow velocities. Specifically, flow into the RV increases during inspiration and decreases with expiration, whereas transmitral velocity decreases with inspiration and increases during expiration. Cardiac catheterization demonstrates elevation and approximate equalization of atrial and diastolic ventricular pressures. In addition, RV systolic pressure rises while LV systolic pressure falls during inspiration, and the opposite occurs during expiration (Figure 1). This “respiratory discordance” is considered by many to be the most specific finding of constrictive pericarditis.
1. What findings on physical examination, cardiopulmonary exercise test, MRI, and cardiac catheterization were helpful in making the correct diagnosis?
Kussmaul’s sign and pericardial knock were helpful physical examination signs pointing to the diagnosis. The cardiopulmonary exercise test showed reduced oxygen pulse and blood pressure at peak exercise, which is consistent with the diagnosis but nonspecific. The MRI demonstrated the septal bounce. The cardiac catheterization was diagnostic, as it demonstrated near-equalization of the end-diastolic pressures in the RV and LV along with dissociation of the RV and LV systolic pressures during the respiratory cycle.
2. How can these findings be explained by the underlying pathophysiology?
All of the above findings are explained by the rigid pericardium that limits myocardial expansion and ventricular filling. The rigid pericardium leads to the pathologic ventricular interdependence and prevents the ventilation induced changes in pleural pressure from being transmitted to the cardiac chambers.
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Author Contributions: T.E.K. and M.J.M. contributed equally to the initial writing and preparation of the manuscript. L.S. contributed to resubmitting the manuscript for second review. L.S. modified the initial manuscript in response to reviewer comments along with modifying the figures.
Author disclosures are available with the text of this article at www.atsjournals.org.
