The clinical presentation of constrictive pericarditis is similar to that of restrictive cardiomyopathy: predominantly signs of systemic venous congestion and less pronounced signs of low cardiac output. The distinction between these two diagnoses is difficult but very important because constrictive pericarditis is treatable, whereas restrictive cardiomyopathy is likely not. This chapter emphasizes the hemodynamic differences and the diagnostic techniques that can be used to differentiate between these two conditions.
Definition and Morphology
Restrictive cardiomyopathy is a disease of the myocardium. The key element is decreased ventricular compliance, whereas ventricular volumes are normal or reduced. Systolic function is often considered to be normal, but contractility is seldom entirely normal. The flow into the ventricles is restricted; there is no problem with filling of the atria. The increased filling pressures required for ventricular filling against a higher resistance will lead to gross enlargement of both atria and marked dilatation of the systemic veins.
Constrictive pericarditis is the end stage of an inflammatory process, leading to scarring of the pericardium. Visceral and parietal pericardium, originally two smooth separate layers, become one rigid case around the entire heart. Most often, but not always, this layer is thickened and can be calcified. The causative inflammatory process may have affected the myocardium as well, leading to decreased ventricular function, but in “pure” constrictive pericarditis the ventricular (myocardial) function is normal—both systolic and diastolic. Because the pericardium encases the whole heart there is restriction to filling of the entire heart, not only of the ventricles. Characteristic findings include normal-sized ventricles, atria that are slightly enlarged, all surrounded by a thickened pericardium and marked dilatation of the systemic veins.
Epidemiology and Genetics
Constrictive pericarditis is a rare, acquired disease. It is more common in men than in women, with a ratio of 2:1. There is no known genetic predisposition and there are no reliable data regarding the occurrence in the general population. Tuberculosis was by the far the most common cause of constrictive pericarditis, and still is in the non-Western world, such as India and Africa and other regions that still have a high prevalence of tuberculosis. Over 60%, even up to 90%, of diagnosed cases of constrictive pericarditis are still caused by tuberculosis in these parts of the world. In the Western world, the incidence of constrictive pericarditis resulting from tuberculosis has dropped. Although the most common form is idiopathic, other causative factors play a more prominent role: chest irradiation, cardiac surgery, pericarditis, and autoimmune disorders. Chest irradiation, mainly for Hodgkin disease, is associated with constrictive pericarditis in up to 4% of cases. Constrictive pericarditis as a complication of cardiac surgery is even more rare: among 5207 adults who underwent cardiac surgery, postoperative constrictive pericarditis was recognized in 11 patients (0.2%). Others also report a very low incidence after cardiac surgery. However, it is a diagnosis that is often missed. Therefore the reported incidence probably underestimates the real incidence.
Restrictive cardiomyopathy is less rare. In the Western world, amyloidosis is by far the most common cause of restrictive cardiomyopathy, accounting for approximately 10% of all nonischemic cardiomyopathies. It is often secondary, but familial forms have been described and account for 10% to 20% of clinically manifest cases. Transthyretin (TTR) is associated with these familial forms of amyloid-related restrictive cardiomyopathy. Inheritance is usually autosomal dominant, but autosomal recessive, X-linked, and mitochondrial-transmitted disease have all been reported. Most identified genes encode sarcomere or Z-disk proteins. Another cause of restrictive cardiomyopathy is endomyocardial fibrosis. It is rare in areas in the world with moderate temperatures, but in the tropics it is a serious health problem. In equatorial Africa it accounts for approximately 20% of all cases of heart failure and up to 15% of cardiac deaths. Environmental and nutritional factors (cassava roots) possibly play an important role in this tropical form of endomyocardial fibrosis. Hypereosinophilic endomyocardial fibrosis, better known as Loeffler endomyocardial fibrosis, is more common in moderate climates but is still considered very rare. If no likely cause of the restrictive cardiomyopathy can be found, the diagnosis of idiopathic restrictive cardiomyopathy is made; a very rare disease.
Early Presentation and Management
In terms of the history and physical examination, constrictive pericarditis is virtually indistinguishable from restrictive cardiomyopathy: congestive heart failure is often the first presentation of both entities. The symptoms are usually dyspnea on mild exertion and fatigue. Chest pain is rare. At physical examination the signs of right-sided heart failure are prominent: jugular vein distention, hepatomegaly, and edema of the legs. In advanced cases, ascites will be present.
Diagnosis
There is no single diagnostic test that has sufficient specificity and sensitivity to differentiate between constrictive pericarditis and restrictive cardiomyopathy. The information that is acquired by all diagnostic modalities, together with a thorough understanding of the pathophysiologic differences between these two diseases, should be used to come to the diagnosis ( Box 62.1 ). Table 62.1 gives an overview of features that are helpful in the differential diagnosis.
No single diagnostic tool or approach leads to 100% certainty in the diagnosis of constrictive pericarditis or restrictive cardiomyopathy in all patients.
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A thorough knowledge of the pathophysiologic differences between constrictive pericarditis and restrictive cardiomyopathy is the most important factor in the eventual diagnosis.
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The integration of pathophysiologic understanding of the diseases with the outcomes of the diagnostic tests is the key to correct diagnosis and, consequently, the right treatment.
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For restrictive cardiomyopathy: Cardiac function and disease progression can be tracked by echocardiography and simple measures of exercise tolerance (eg, the 6-min walk). Symptoms are an imprecise guide, particularly after initial stabilization.
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An evaluation and plan should be made for women with respect to the feasibility of pregnancy.
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There is great heterogeneity in familial forms of restrictive cardiomyopathy. A familial pattern should be actively sought by screening relatives of the proband, who may benefit from earlier detection.
| Feature | Constrictive Pericarditis | Restrictive Cardiomyopathy |
|---|---|---|
| Past medical history | Previous pericarditis, cardiac surgery, trauma, radiotherapy, connective tissue disease | Items in previous column rare |
| Jugular venous waveform | Dips in x and y troughs brief and “flicking”; not conspicuous positive waves | Dips in x and y troughs less brief; may have conspicuous a wave or v wave |
| Extra sounds in diastole | Early S3, high-pitched “pericardial knock,” no S4 | Later S3, low-pitched “triple rhythm,” S4 in some cases |
| Mitral or tricuspid regurgitation | Usually absent | Often present |
| Electrocardiogram | P waves reflect intra-atrial conduction delay. Atrioventricular or intraventricular conduction defects are rare | P waves reflect right or left atrial hypertrophy or overload. Atrioventricular or intraventricular conduction defects are not unusual |
| Plain chest radiography | Pericardial calcification in 20% to 30% | Pericardial calcification rare |
| Ventricular septal movement in diastole | Abrupt septal movement (notch) in early diastole in most cases | Abrupt septal movement in early diastole seen only occasionally |
| Ventricular septal movement with respiration | Notable movement toward left ventricle in inspiration usually seen | Relatively little movement toward left ventricle in most cases |
| Atrial enlargement | Slight or moderate in most cases | Pronounced in most cases |
| Respiratory variation in mitral and tricuspid flow velocity | >25% in most cases | <15% in most cases |
| Respiratory variation of hepatic vein a wave reversal | Increase on expiration | Increase on inspiration |
| Mitral inflow velocity | E-wave velocity normal to high E/E’ often low (to normal) | E-wave velocity low (to almost normal) E / E ′ substantially elevated |
| Equilibration of diastolic pressures in all cardiac chambers | Within 5 mm Hg in nearly all cases; often essentially the same | Within 5 mm Hg in a small proportion of cases |
| Dip-plateau waveform in the right ventricular pressure waveform | End-diastolic pressure more than one third of systolic pressure in many cases | End-diastolic pressure often less than one third of systolic pressure |
| Peak right ventricular systolic pressure | Nearly always <60 mm Hg, often <40 mm Hg | Frequently >40 mm Hg and occasionally >60 mm Hg |
| Discordant respiratory variation of ventricular peak systolic pressures | Right and left ventricular peak systolic variations are out of phase | Right and left ventricular peak systolic pressure variations are in phase |
| Paradoxical pulse | Often present to a moderate degree | Rarely present |
| MRI or CT | Shows thick pericardium in most cases | Shows thick pericardium only rarely |
| Endomyocardial biopsy | Normal or nonspecific abnormalities | Shows amyloid in some cases; rarely other specific infiltrative disease |
Pathophysiology
Ventricular filling is restricted in both constrictive pericarditis and restrictive cardiomyopathy, leading to raised atrial pressures in both. High atrial pressures in the case of restrictive cardiomyopathy will lead to (often gross) atrial enlargement. Atrial dilatation is limited in constrictive pericarditis because of the rigid pericardium, which also encapsulates the atria.
At the onset of diastole, at the time of atrioventricular valve opening, the high atrial pressures will lead to a rapid early ventricular filling. Myocardial compliance is normal in constrictive pericarditis, but ventricular filling is soon halted by the pericardial constraint. In restrictive cardiomyopathy it is the stiff myocardium with its decreased compliance that causes the restriction to ventricular filling. The mechanisms differ, but the effect is the same: ventricular diastolic pressures will increase sharply after the small increase in volume that occurs during early filling. This is represented by the typical “square root” or “dip and plateau” appearance of ventricular pressure curves that constrictive pericarditis and restrictive cardiomyopathy have in common ( Fig. 62.1 ). At the moment when ventricular pressure equals atrial pressure, atrioventricular flow will stop. This happens at the end of the early filling period. More subtle differences between restrictive cardiomyopathy and constrictive pericarditis can be seen when myocardial function is studied in detail. In constrictive pericarditis, the velocity of early relaxation of ventricular myocardium is entirely normal, or even faster than normal. The myocardium itself is not diseased. In restrictive cardiomyopathy, as in all forms of cardiomyopathy, the myocardium is affected and this is shown by the decreased velocity of early relaxation. This can be visualized by tissue Doppler or strain-rate imaging.
In a normal heart, differences in diastolic pressures can exist between left- and right-sided chambers, because of differences in their individual compliance. In patients with constrictive pericarditis this individual compliance is overruled by a common restrictive force: the rigid pericardium. The entire heart now functions as a single cylinder, allowing only marginal differences in intracardiac diastolic pressure between the individual chambers. This equalization of pressures is, together with the “square root” sign, the hallmark of a restrictive physiology in constrictive pericarditis. However, very similar patterns can also be seen in restrictive cardiomyopathy.
It was the breakthrough work of Hatle et al. in 1989 that illuminated the hemodynamic changes with respiration that occurred in constrictive pericarditis but not in restrictive cardiomyopathy: (1) dissociation between intrathoracic and intracardiac pressure and (2) enhanced ventricular interaction. In the heart with a normal pericardium, inspiration causes a decrease in pressure of all intrathoracic structures, including the heart. Because the pulmonary veins, left atrium, and left ventricle are all equally affected by these changes in intrathoracic pressure, there will be no change in driving force from the pulmonary veins to the left atrium and left ventricle. This is true also for patients with restrictive cardiomyopathy. In contrast, in constrictive pericarditis, the rigid pericardium shields the intracardiac chambers from these respiration-related changes in intrathoracic pressure. During inspiration, the pressure in the pulmonary veins decreases, whereas pressure in the left atrium and left ventricle remains unaltered. The diminished driving force during inspiration results in less filling of the left side of the heart. During expiration, the opposite occurs.
Enhanced ventricular interaction is the second effect of pericardial restraint, but is closely related to the first. At inspiration, the driving force for left ventricular (LV) filling is decreased, whereas the driving forces for filling of the right ventricle increase: the lowering of the intrathoracic pressure will lead to increased systemic venous return. The combination of decreased LV filling and increased systemic venous return will allow increased right ventricular (RV) filling at inspiration. This situation is responsible for the “septal bounce” that can be seen with cardiac imaging: the sudden shift of the interventricular septum toward the left ventricle at the beginning of inspiration.
Past Medical History
In the population of adults with congenital heart disease, many will have had cardiac surgery in the past. Scarring of the pericardium is always reported as a possible cause of constrictive pericarditis. However, on the basis of the (sparse) data regarding the incidence of constrictive pericarditis after cardiac surgery, there is little chance of ever diagnosing one. Chest irradiation can cause both diseases. A history of connective tissue disease is compatible with constrictive pericarditis. A (family) history of amyloidosis is suggestive of restrictive cardiomyopathy.
Physical Examination
The central venous pressure is raised. In the distended jugular veins the two dips—the x and y troughs, respectively, in systole and early diastole—are more prominent than normal in both constrictive pericarditis and restrictive cardiomyopathy. The atrial contraction is often more forceful in restrictive cardiomyopathy than in constrictive pericarditis, reflected by a large—and clearly visible— a wave in the jugular vein, not seen in constrictive pericarditis. At auscultation, a third heart sound can be heard in both diseases. Audible mitral regurgitation is often present in restrictive cardiomyopathy but rarely in constrictive pericarditis.
Biomarkers
If a patient presents with signs of diastolic heart failure or right-sided heart failure and the B-type natriuretic peptide (BNP) is normal, idiopathic constrictive pericarditis should be considered. Patients with restrictive cardiomyopathy usually have a substantially elevated BNP, but so do patients with secondary constrictive pericarditis, eg, after radiation or cardiac surgery. BNP is usually higher in restrictive cardiomyopathy, but the overlap with BNP values in the group of secondary constrictive pericarditis is such that it does not discriminate between the two disease entities.
Electrocardiography
The typical electrocardiogram (EKG) pattern in constrictive pericarditis is a normal QRS axis, low voltage, and generalized T-wave flattening or inversion, but in restrictive cardiomyopathy the voltages of the QRS complexes are also usually low. If patients with restrictive cardiomyopathy are in sinus rhythm, biatrial enlargement can be seen, but patients will more often have atrial fibrillation because of the severe atrial enlargement. EKG patterns can give a clue, but are not specific enough, with too many exceptions, to be helpful in the discrimination between the two disease entities.
Chest Radiography
Pericardial calcification on a chest radiograph in patients with heart failure suggests constrictive pericarditis. In the past it was often observed with tuberculous pericarditis. However, because the incidence of tuberculosis has decreased in Western countries, pericardial calcification is often associated with idiopathic pericardial disease. Pericardial calcification is not a feature of restrictive cardiomyopathy.
Two-Dimensional and Doppler Echocardiography
Two-dimensional (2D) echocardiography is particularly helpful in the exclusion of other causes of right-sided heart failure, which include LV systolic dysfunction, mitral valve dysfunction, RV infarction, pulmonary stenosis, and pulmonary hypertension. Hepatic vein and inferior caval vein distension will be present in right-sided heart failure, irrespective of the causative mechanism.
Both restrictive cardiomyopathy and constrictive pericarditis will have signs of restriction to ventricular filling. Doppler tracings of inflow patterns of both the mitral and tricuspid valves will reflect the fact that ventricular filling occurs only early in diastole. The velocity of the early filling—the E-wave—is high, but the duration is short, represented by a short deceleration time. Because the end-diastolic pressure in the ventricles is extremely high, atrial contraction will not produce atrial pressures that are higher than the end-diastolic ventricular pressures: atrial contraction will contribute little to ventricular filling and the velocity of the a wave will be low.
There are a few features that allow discrimination by means of echocardiography between the two conditions:
- a.
Myocardial properties are different between constrictive pericarditis and restrictive cardiomyopathy.
- b.
Effect of respiration on ventricular filling is very abnormal in constrictive pericarditis and not (or less) abnormal in restrictive cardiomyopathy.
Myocardial Properties
In restrictive cardiomyopathy, the myocardium itself is affected, and this is visible when myocardial velocities are measured. Myocardial strain imaging (speckle tracking) will show lower amplitudes of longitudinal strain in restrictive cardiomyopathy than in constrictive pericarditis, but the differences in myocardial velocities at the level of the mitral valve, measured by tissue Doppler, are more striking. The E-wave velocity is normal to high in constrictive pericarditis and low (to almost normal) in restrictive cardiomyopathy. E / E ′, often used as an indicator of diastolic function, is often low (to normal) in constrictive pericarditis and substantially elevated in restrictive cardiomyopathy. A patient with diastolic heart failure, signs of restrictive filling, a high velocity of early ventricular filling of both blood Doppler and tissue Doppler, and a normal to low E / E ′, will have constrictive pericarditis and not a myocardial disease such as restrictive cardiomyopathy. As with all measurements, there is some overlap, and additional imaging is often necessary to be sure about the discrimination between the two conditions.
Effect of Respiration on Ventricular Filling
In constrictive pericarditis, the rigid pericardium isolates the entire heart from other intrathoracic structures (lungs, pulmonary veins, systemic veins) and condemns the structures that lie within the rigid pericardium to share this limited and unyielding space.
At inspiration, the intrathoracic pressure drops, normally 5 to 10 mm Hg, but the left atrium and left ventricle are shielded from this lowering of pressure by the rigid pericardium. The lower pulmonary venous pressure will hamper filling of the left atrium, and consequently the left ventricle, during systole. Left atrial filling by pulmonary venous flow is less, seen by lower velocities of pulmonary venous flow measured with Doppler. A marked decrease—often more than 25%—of the E-wave velocity across the mitral valve is seen in the first beat after beginning of the inspiration. At expiration, when the intrathoracic pressure is higher, and consequently the filling pressures of the left atrium are higher, more forward flow occurs in the pulmonary veins. There will be more ventricular filling, almost exclusively taking place in early diastole, visible as a substantially higher flow velocity across the mitral valve. Using 2D echo, respiratory changes of ventricular filling can be appreciated, eg, from the apical four-chamber view, with a sudden shift of the interventricular septum (“septal bounce”) toward the right (at expiration) or the left (at inspiration). With M-mode, or color-coded M-mode, the timing of the interventricular septal movements can be better appreciated. This is an underused but very valuable tool in clinical practice ( Fig. 62.2 ).
