Constrictive Pericarditis and Restrictive Cardiomyopathy

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.

BOX 62.1

Diagnosis

No single diagnostic tool or approach leads to 100% certainty in the diagnosis of constrictive pericarditis or restrictive cardiomyopathy in all patients.

A thorough knowledge of the pathophysiologic differences between constrictive pericarditis and restrictive cardiomyopathy is the most important factor in the eventual diagnosis.
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.
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.
An evaluation and plan should be made for women with respect to the feasibility of pregnancy.
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.

TABLE 62.1

Features Useful in Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy

From Hancock EW. Differential diagnosis of restrictive cardiomyopathy and constrictive pericarditis. Heart . 2001;86:343-349, with permission.

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

CT, Computed tomography; MRI, magnetic resonance imaging.

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.

Figure 62.1, A, Simultaneous left ventricular (LV) and right ventricular (RV) pressure recording in a patient with constrictive pericarditis showing the typical “square root” sign as well as equalization of diastolic pressures. B, Equalization of pressures on simultaneous right atrial (RA) and LV diastolic pressure tracing.

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.

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