Pericardial Disease

Acute Pericardial Disease

The pericardium comprises two layers; the visceral layer that adheres to epicardial surface of the heart, and the parietal layer that surrounds most of the heart. Pericardial disease is common, and diagnosis is usually straightforward as the pericardium reacts to disruption by a wide variety of agents and processes in a relatively uniform manner. Typical presentation is with chest pain and fever, production of pericardial fluid with possible cardiac tamponade, or a constrictive pattern by thickening, retraction and calcification.

Cardiac Tamponade

An increase in intrapericardial pressure, resulting in compression of the heart, and thereby a resitriction of cardiac inflow, is termed cardiac tamponade. Tamponade may result from pericardial effusion of any cause. The intrapericardial pressure importantly determines to what extent cardiac inflow is decreased, but two factors need to be taken into consideration. First, intrapericardial pressure is determined not only on the amount of fluid that accumulates, but also on the rate with which this accumulation proceeds, and the available distensibility of the pericardium. Chronic effusions may therefore lead to small increases in intrapericardial pressures in the presence of large fluid accumulations, and small accumulations may directly lead to severe cardiac tamponade for example after free wall rupture. Second, the intravascular volume and intra-atrial, and -ventricular pressures determine at what pressure inflow becomes impaired. When intrapericardial pressure exceeds right atrial pressure (approximately 8 mmHg), tamponade typically follows. However, in patients in whom intra-atrial pressure is decreased, for example due to volume depletion, tamponade may already occur at lower intrapericardial pressures; low-pressure cardiac tamponade.

With increasing intrapericardial pressure, clinical features increase with severe hemodynamic compromise as its end stage. First, small changes in intrapericardial pressure induce subtle changes in arterial pressure, cardiac output, and variations in arterial pressure with inspiration (pulsus paradoxus). When intrapericardial pressure reaches levels similar to right atrial and diastolic right ventricular pressure echocardiographic evidence of tamponade may be found in diastolic collapsing of the right atrium, and increased variations of blood flow velocity over the cardiac valves with respiration. Fulminant clinical tamponade presents with symptoms that depend on its etiology. Acute cardiac tamponade based upon aortic or free wall rupture presents with syncope and sudden collapse, whereas tamponade in the setting of an acute inflammatory pericardits may present with pericardial chest pain, and dyspnoea. Therefore, in patients presenting with chest discomfort, dyspnoea, tachycardia or tachypnoea, cardiac tamponade should be suspected when jugular distension, hypotension or pulsus paradoxus is present. Auscultation may reveal pericardial friction rub, and heart sounds may be faint. Echocardiography shows pericardial effusion, the previously mentioned diastolic collapsing of the cardiac cavities, increased flow velocity over tricuspid and pulmonary valves, and decreased flow velocity over the aortic and mitral valves.

When secondary to inflammatory pericarditis, tamponade up to moderate severity may be treated by anti-inflammatory drugs. In severe tamponade, pericardiocentesis should be performed to immediately alleviate intrapericardial pressure. Surgical drainage should be considered when pericardiocentesis is unsuccessful, or when tamponade recurs.

Acute pericarditis

Acute inflammation of the pericardium may result from a wide variety of etiologies (Table 1), and typically presents with chest pain, a pericardial friction rub on auscultation, and repolarization changes on the electrocardiogram.

Table 1. Causes of acute pericarditis
Acute idiopathic pericarditis Infectious pericarditis: Viral Tuberculosis Bacterial Others Postpericardiotomy syndrome Postmyocardial infarction pericarditis Renal insufficiency Neoplastic disease Chest trauma Irradiation Collagen diseases

Patients present with a rapid-onset chest pain syndrome located precordial and retrosternal, and radiating to the subclavian region, the back and the trapezoid region. Chest pain is of moderate severity, lasting for several days, and increases with inspiration or chest movement. Patients typically alleviate the pain by sitting and leaning forward.

A pericardial friction rub is pathognomonic of pericarditis, and ECG changes are frequently present, which comprise diffuse concave ST-segment elevation, with positive T-waves in several leads. Atrial injury is accompanied by PR-segment depression. After several hours to a few days, ST-segments return iso-electric, and negative T-waves may occur subsequently, which may persist for several weeks although they frequently normalize within days. Pericardial effusion may be present, and can be diagnosed by chest X-ray when fluid accumulation exceeds 250mL, or by echocardiography.

Although initial presentation may mimic ST-segment elevation myocardial infarction (STEMI). Onset of chest pain is less abrupt in acute pericarditis, and varies with respiration. Furthermore, diffuse ST-segment changes are present in pericarditis, whereas STEMI presents with ST-segment elevation, and reciprocal depression, in leads corresponding to the ischemic myocardium. Biomarkers can be positive in both syndromes.

Treatment consists of aspirin while pain and fever are present, which usually adequately alleviates symptoms. Another option is NSAIDs, which are recommended when aspirin in insufficient or contraindicated. Corticosteroids should, however, be avoided as they are associated with relapsing pericarditis. Hospital admission may be necessary in patients with high fever, large effusions or cardiac tamponade.

Recurrent pericarditis

In 8 to 80% of patients, pericarditis recurs after a first episode of acute pericarditis. A continuous type, in which symptoms recur shortly after cessation of anti-inflammatory therapy, and an intermittent type, in which symptom-free periods of more than 6 weeks separate recurrences, can be distinguished. Frequently resulting from inadequate therapy or corticosteroid-use during the initial episode, subsequent recurrences are usually less severe. A recurrence should be treated according to the same procedures as for the first event. Pericardiectomy may be considered the last resort in severely refractory recurrent pericarditis, but its results are unpredictable. Prognosis of the disease is excellent, as severe complications are rare.

Pericardial effusion

Fluid accumulation in the pericardium, pericardial effusion, is a common finding on routine echocardiography, and is asymptomatic in the absence of inflammation or cardiac tamponade. It may result from any disease of the pericardium, or be iatrogenic. Most frequently it results from idiopathic pericarditis, malignancy, or iatrogenic defects (Table 2).

Table 2. Causes of pericardial effusion
Any type of acute pericarditis Cardiac surgery Acute myocardial infarction Heart failure Chronic renal failure Iatrogenic Metabolic diseases Autoimmune diseases Trauma Chylopericardium Pregnancy Idiopathic

Where the use of electrocardiography and chest radiography is limited in pericardial effusion, echocardiography may reveal an echo-free space in the anterior or posterior sacs, present throughout the cardiac cycle. The absence of cavity collaps indicates the absence of tamponade.

Treatment of pericardial effusion depends on the extent of symptoms, and the etiology underlying the effusion. Asymptomatic mild pericardial effusion (<10mm sum of echo-free spaces in anterior and posterior sacs) may be left untreated. Control echocardiography is indicated at 3-6 months. In moderate (10-20mm sum of echo-free space) to large effusions, a complete history, routine physical examination, ECG, chest radiography and routine blood analysis is indicated. Treatment is then based upon its expected etiology, standard treatment with aspirin or NSAIDs to relief pain, with invasive procedures indicated in case of tamponade with hemodynamic compromise or recurrent pericarditis as discussed previously. Specific etiologies of pericardial effusion must be managed accordingly.

Chronic pericardial effusion

Pericardial effusion is considered chronic when moderate to large effusions persist for at least 3 months. Resulting most frequently from idiopathic cause, intrapericardial pressure is frequently elevated in these patients, which may lead to unexpected tamponade in up to 30% of patients. Hence, pericardiocentesis is indicated to alleviate the fluid accumulation, and pericardiectomy should be considered when large effusions recur. Long term outcome is excellent with this approach.

Constrictive pericarditis

The pericardial layers may become rigid, thickened, and may fuse, resulting in restriction of cardiac filling; constrictive pericarditis. In contrast to cardiac tamponade, where cardiac is hampered throughout diastole, cardiac filling is prohibited in the last two-thirds of diastole in constrictive pericarditis, with preserved abrupt filling in early diastole.

Chronic constrictive pericarditis

Any form of pericarditis may end in constrictive pericarditis, presenting with chronic fatigue, dyspnoea, jugular distension, proto-diastolic pericardial knock, hepatomegaly, ascites, peripheral oedema, and pleural effusion. Atrial fibrillation is a common finding, and diffuse flattened or negative T-waves are usually present. These suggestive clinical findings, in addition to a physiology of restriction or constriction on echocardiography, and the presence of a thickened pericardium provide the diagnosis. However, a thickened pericardium may be absent, which does not rule out constrictive pericarditis. Pericardiectomy is the only effective treatment, which should be instituted shortly after diagnosis, as surgical mortality increases with increasing age and functional impairment.

Table 3. Differential diagnosis between chronic constrictive pericarditis and restrictive cardiomyopathy
Constrictive pericarditis	Restrictive cardiomyopathy
Physical examination
Early diastolic precordial impulse	Apical impulse may be prominent
Pericardial knock
No murmur	Third sound may be present Regurgitant murmur common
Electrocardiography
Low voltage Frequent atrial fibrillation Normal QRS complex	Low voltage in amiloidosis Frequent atrial fibrillation Bundle branch block
Chest radiogram
Pericardial calcification possible	Non-specific cardiomegaly
Echocardiography
Normal wall thickness	Pericardial thickening
Diastolic notch of interventricular septum
Increased wall thickness (amyloidosis)	Enlarged left and right atria
Doppler studies e' septal =8 cm/sec and normal S' mitral annular velocity
Mitral inflow increase during expiration Mitral flow propagation velocity M-mode colour =45cm/s Increased diastolic flow reversal in the hepatic vein with expiration e' septal <8cm/s and decreased mitral annular velocity	Mitral inflow velocity without respiratory variation Mitral flow propagation velocity M-mode colour <45cm/s Increased diastolic flow reversal in the hepatic vein with inspiration
Cardiac catheterization
RVEDP and LVEDP usually equal RV systolic pressure <50mmHg	RVEDP >one-third of RV systolic pressure LVEDP often >5mm greater than RVEDP
Endomyocardial biopsy
Normal or non-specific changes	May reveal specific causes
CT/MR imaging
Pericardium thickened or calcified	Normal pericardium
CT, computer tomography; e', e wave velocity by tissue velocity imaging;
LVEDP, left ventricular end-diastolic pressure; MR, magnetic resonance;	RV, right ventricular; RVEDP, right ventricular end-diastolic pressure.

Subacute elastic constriction

Elastic cardiac constriction, in contrast to the rigid chronic constriction, results from an elastic thickened pericardium, which still allows distension during the respiratory cycle. It may be seen in the first period after acute inflammatory or infectious pericarditis, and may progress to chronic pericardial constriction, or prove to be a transient process.

Effusive-constrictive pericarditis

Presenting with cardiac tamponade on admission, effusive-constrictive pericarditis is characterized by a persistent increase in right atrial and end-diastolic ventricular pressures after intrapericardial pressure has been alleviated by pericardiocentesis. Apart from idiopathic cases, it may accompany chest radiation, cardiac surgery, neoplasia, and tuberculosis. Most frequently, the disease will progress to persistent constriction for which epicardiectomy is indicated, but it may rarely be a transient phenomenon.

Transient cardiac constriction

Clinical and hemodynamic features of constrictive pericarditis may dissipate spontaneously, which is seen commonly (20%) in idiopathic acute pericarditis with effusion, but may also be seen in tuberculous and purulent pericarditis. Hence, a primarily conservative approach may alleviate the need for epicardiectomy.

Specific types of pericardial disease

Infectious pericarditis

Idiopathic/Viral pericarditis

This is the most frequent form of pericarditis, accounting for more than 80% of cases, of which most probably are of viral etiology, but virus identification is cumbersome and no treatment consequences exist. The disease is frequently accompanied by pericardial effusion, cardiac tamponade, and left pleural effusion, but prognosis is notably good.

Tuberculous pericarditis

Predominantly found in developing countries, and in patients with human immunodeficiency virus (HIV) infection, tuberculous pericarditis is rare in the Western world and presents typically with symptoms of acute pericarditis. Identification of Mycobacterium tuberculosis yields the diagnosis, which may be found in pericardial or other bodily fluids, or may be assumed when caseating granulomas are found. Routine tuberculosis treatment, comprising three antituberculous agents, yields a good prognosis although a subacute constrictive pericarditis is common, requiring pericardiectomy but with excellent outcome.

Purulent pericarditis

Purulent pericarditis has a high mortality, owing to the intangible diagnosis and the related severity of the underlying disease. Cardiac tamponade is frequent, and acute constrictive pericarditis may occur. The disease should be considered in all patients presenting with high fever, dyspnoea, and tachycardia with intrathoracic or subphrenic infections, or sepsis with symptoms that suggest pericardial involvement. Pericardiocentesis is indicated even in the absence of tamponade when the disease is confirmed, and appropriate antibiotic treatment should be instituted. Long-term prognosis is however excellent in patients that survive until discharge.

Post myocardial infarction pericarditis

Pericardial effusion frequently occurs in the early stage after myocardial infarction, which remains asymptomatic and can be left untreated. Within the first week after myocardial infarction, acute pericarditis may occur, which is related to the extent of the infarction. The presence of a pericardial rub may distinguish chest pain and ECG changes resulting from acute pericarditis from recurrent ischemia.

Weeks to months after myocardial infarction, pleuropericarditis of autoimmune nature may prevail, termed Dressler’s syndrome. However, this syndrome is rare, and treatment with corticosteroids yields a good prognosis.

Neoplastic pericarditis

Lung cancer is the most frequent cause of neoplastic pericarditis. Cardiac tamponade in patients with a history of malignancy, in the absence of inflammatory signs indicates a possible malignant etiology, as is lack of response to NSAIDs in this patient group. When the effusion is indeed of malignant origin (approximately 40% of cases), treatment aims at alleviation of symptoms and the prevention of recurrences. A balance should be sought between pericardiocentisis in which recurrence is frequent, and pericardiectomy, which may be overly aggressive in this critically ill subset of patients.

Hypothyroidism

With increasing severity of primary hypothyroidism, the prevalence of pericardial effusion increases. Thyroid hormone replacement therapy results in remission of the effusion.

Post-pericardiotomy pericarditis

Pericarditis is common after cardiac surgery (18%), of which the etiology is unclear although an autoimmune origin has been proposed. In contrast to other forms of pericarditis, post-pericardiotomy pericarditis may be effectively treated with corticosteroids and NSAIDs.