Chylopericardium and cholesterol pericarditis

INTRODUCTION — 

A pericardial effusion is the accumulation of fluid within the pericardial sac surrounding the heart that exceeds the small physiologic amount that is normally present (15 to 50 mL). Pericardial effusion can develop in patients with virtually any condition that affects the pericardium, including acute pericarditis and a variety of systemic disorders. (See "Pericardial effusion: Approach to diagnosis" and "Etiology of pericardial disease".)

Chylopericardium (pericardial effusion composed of chyle) and cholesterol pericarditis (pericardial inflammation with pericardial effusion containing cholesterol crystals and inflammatory cells) will be reviewed here. The distinction between chylopericardium and cholesterol pericarditis is analogous to that between chylothorax and cholesterol pleural effusion (pseudochylothorax). (See "Etiology, clinical presentation, and diagnosis of chylothorax" and "Clinical presentation, diagnosis, and management of cholesterol pleural effusions".)

Other causes of pericardial effusion and pericarditis are discussed separately. (See "Etiology of pericardial disease" and "Pericardial effusion: Approach to diagnosis", section on 'Identifying the etiology'.)

CHYLOPERICARDIUM — 

Chylopericardium is a pericardial effusion comprised of chyle, the normal content of the lacteals (lymphatics of the small intestine) and the thoracic duct, which carries chyle from the intestinal tract to the blood stream (figure 1) [1]. Although wide anatomic variation exists, in most persons the thoracic duct passes in relatively close proximity to the pericardium over its course from the cisterna chyli to the jugular and subclavian veins.

Etiology of chylopericardium — Chylopericardium may be primary (idiopathic) or secondary. A literature review identified 98 cases of chylopericardium in 95 articles published between 1946 and May 2021 [2]. Sixty percent of these cases were considered primary.

●Primary (idiopathic) chylopericardium is a diagnosis made after exclusion of secondary causes [3-8].

●Secondary chylopericardium usually results from injury or disruption of the thoracic duct (which may cause abnormal communication between the thoracic duct and the lymphatics of the pericardium) or obstruction of chyle (due to distal obstruction of the thoracic duct or the subclavian vein). Causes of secondary chylopericardium include [2,9-12]:

•Iatrogenic:

-Thoracic or cardiac surgery (especially for congenital heart disease) [13-18]

-Radiation therapy

•Mediastinal neoplasms (eg, lymphoma, signet ring carcinoma). (See "Clinical presentation and initial evaluation of non-Hodgkin lymphoma" and "Classic Hodgkin lymphoma: Presentation, evaluation, and diagnosis in adults".)

•Central vein thrombosis. (See "Overview of thoracic central venous obstruction".)

•Trauma (blunt or penetrating).

•Congenital disorders of the lymphatic system (eg, lymphangiomatosis, cystic hygroma). (See "Enlarged nuchal translucency and cystic hygroma".)

•Inflammatory disorders (eg, Behçet syndrome). (See "Clinical manifestations and diagnosis of Behçet syndrome".)

•Infection (eg, tuberculosis). (See "Diagnosis of pulmonary tuberculosis in adults".)

•Acute pancreatitis. (See "Clinical manifestations, diagnosis, and natural history of acute pancreatitis".)

•Gorham disease. (See "Treatment for tenosynovial giant cell tumor and other benign neoplasms affecting soft tissue and bone", section on 'Gorham disease'.)

Clinical manifestations

Initial features — The presence of a pericardial effusion may be suspected from the history, physical examination, electrocardiogram (ECG), and chest radiograph, and confirmed by echocardiography. (see "Pericardial effusion: Approach to diagnosis", section on 'Diagnostic approach').

●Symptoms and signs – Some patients have symptoms of acute pericarditis including chest discomfort or symptoms related to the underlying etiology (such as fever in patients with infection), although some patients are asymptomatic [2]. Chronic leakage of chyle is typically associated with significant systemic illness.

A minority of patients with chylopericardium present with dyspnea, elevated jugular venous pressure, pulsus paradoxus, hypotension, and other signs of cardiac tamponade [2,19]. (See 'Complications' below and "Cardiac tamponade".)

●Electrocardiogram – Patients who present with acute pericarditis may have diffuse ST elevation and PR depression, as described separately (figure 2 and waveform 1). (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram'.)

For patients with cardiac tamponade, common ECG findings include sinus tachycardia, low QRS voltage, and electrical alternans (waveform 2). (See "Cardiac tamponade", section on 'Electrocardiogram'.)

●Chest radiograph – The findings on chest radiograph are variable, depending on the etiology and size of the effusion and underlying comorbidities. Small to moderate effusions may not result in significant findings on the chest radiograph, while larger pericardial effusions typically present with an enlarged cardiac silhouette with clear lung fields (image 1). (See "Pericardial effusion: Approach to diagnosis", section on 'Chest radiograph'.)

The chest radiograph may show evidence of unilateral or bilateral pleural effusion since chylopericardium is sometimes accompanied by chylothorax (chylous pleural effusion). Chylothorax is discussed separately. (See "Etiology, clinical presentation, and diagnosis of chylothorax".)

Complications

●Pericardial complications

•Cardiac tamponade – Chylopericardium can cause cardiac tamponade (with associated symptoms and signs of dyspnea, tachypnea, elevated jugular venous pressure, tachycardia, narrow pulse pressure, and hypotension) [2]. As with any pericardial effusion, the risk of cardiac tamponade depends upon the rate and duration of pericardial fluid accumulation. Acute leakage of chyle, as may occur following trauma, can result in rapid pericardial fluid accumulation and increasing intrapericardial pressure resulting in cardiac tamponade, while chronic leakage of chyle is typically associated with a less acute clinical presentation (figure 3). (See "Cardiac tamponade".)

•Constrictive pericarditis – Constrictive pericarditis is a rare complication of chylopericardium [2,20,21]. (See 'Clinical manifestations' above and "Cardiac tamponade".)

●Other complications – Significant leakage of chyle can cause serious malnutrition, metabolic derangements, and immunologic incompetence. Rarely, expectoration of chyle (chyloptysis) may accompany chylopericardium [22].

Imaging — Presence of a pericardial effusion is generally confirmed by echocardiography. In patients with chylopericardium, the pericardial effusion is most commonly large, though some patients present with moderate or small effusions [2].

Chest computed tomography (CT) is commonly performed in patients with chylopericardium to assess for possible causes, such as mediastinal malignancy. On CT, a chylous pericardial effusion has low or negative Hounsfield units (HU) values [1,23], in contrast to 5 to 40 for exudative effusions and >20 HU for proteinaceous/hemorrhagic pericardial effusions [1,24].

Diagnosis

●When to suspect chylopericardium – The diagnosis of chylopericardium may be suspected in patients with a pericardial effusion and history of trauma or injury to the thoracic duct or other cause of chylopericardium. (See 'Etiology of chylopericardium' above.)

●Pericardial fluid sampling – In patients with cardiac tamponade, the pericardial effusion is drained for therapeutic purposes and the pericardial fluid is analyzed. Pericardial fluid drainage and analysis is also performed in patients with suspected chylopericardium or other suspected causes for which pericardial fluid analysis may alter management (algorithm 1). (See "Pericardial effusion: Approach to diagnosis", section on 'Pericardial fluid analysis and biopsy'.)

●Pericardial fluid analysis – The presence of chylopericardium is suggested by identification of a milky white, opaque, and opalescent pericardial fluid sampled by either pericardiocentesis or surgical pericardial drainage (picture 1). (See "Pericardial effusion: Approach to diagnosis", section on 'Evaluation' and "Pericardial effusion: Approach to management", section on 'Choice of pericardial drainage procedure'.)

The diagnosis of chylopericardium is confirmed by pericardial fluid analysis, which typically reveals [25]:

•Triglyceride level greater than 500 mg/dL (5.65 mmol/L) and cholesterol/triglyceride ratio of less than 1. In a series reporting pericardial fluid results for 98 patients with chylopericardium, the mean cholesterol level was 105 (interquartile range [IQR] 55 to 136) mg/dL and the mean triglyceride level was 874 mg/dL (IQR 552 to 1351) [2].

•Fat globules identified on Sudan 111 staining.

•Negative cultures and no malignancy identified on cytology.

•Lymphocyte predominance (primarily T lymphocytes) on cytologic examination. The lymphocyte count ranges between a few hundred to several thousand per milliliter.

•The electrolyte concentrations are similar to plasma.

•The protein content exceeds 3 g/dL and the specific gravity is also characteristically high.

Differential diagnosis — The differential diagnosis of a milky white pericardial effusion is limited and generally includes cholesterol pericarditis and purulent pericardial effusions.

●Cholesterol pericarditis is distinguished from chylopericardium by the presence of cholesterol crystals and a lower triglyceride concentration. (See 'Cholesterol pericarditis' below.)

●A purulent pericardial effusion, typically resulting from bacterial or tuberculous infection involving the pericardium, may also appear whitish on fluid sampling. However, a purulent effusion is differentiated from chylopericardium by the cellular content (more neutrophils than lymphocytes), cultures for the causative organism, and significantly lower triglyceride levels than seen with chylopericardium.

Identification of leakage site — Imaging of the lymphatic system is performed to delineate thoracic duct anatomy and identify the potential site of chyle leak, as this informs the surgical approach to treatment. Lymphangiography (with planar and CT imaging), lymphangioscintigraphy (with single photon emission CT combined with integrated low-dose CT [SPECT/CT]) [1], or dynamic contrast-enhanced magnetic resonance lymphangiography [26] can be used to help identify an injury or blockage of the thoracic duct (image 2) [27]. These lymphatic imaging techniques are discussed further separately. (See "Etiology, clinical presentation, and diagnosis of chylothorax", section on 'Advanced lymphatic imaging'.)

Management — Management for chylopericardium depends on whether cardiac tamponade is present as well as the underlying etiology.

Pericardial fluid drainage — As noted above, pericardial fluid drainage is a component of the diagnosis and/or management of chylopericardium (algorithm 1). Following therapeutic or diagnostic pericardial fluid drainage, catheter drainage is continued until the volume of flow is <25 mL/day.

Patients with cardiac tamponade require urgent pericardial fluid drainage to alleviate symptoms and prevent hemodynamic collapse. (See "Cardiac tamponade", section on 'Management'.)

Some patients have large uncontrolled pericardial effusion (average daily loss of chyle of 500 mL/day for five days) and require prolonged pericardial drainage.

General measures — All patients with confirmed chylopericardium receive general management including [1,2,25,28]:

●Treatment of the underlying condition – This includes treatment of conditions such as central vein thrombosis, infection (eg, tuberculosis), or inflammatory disorders that may be causing chylopericardium. (See "Primary (spontaneous) upper extremity deep vein thrombosis".)

●Fluid and electrolyte replacement.

●Nutritional intervention to reduce chyle flow – Limited data from case series are available to guide nutritional intervention for chylopericardium [1,2,25,28].

•For patients presenting with cardiac tamponade or >500 mL/day of chyle drainage, we suggest total parenteral nutrition (TPN). The abrupt decline in chyle flow with TPN may prevent nutritional deficiencies and promote healing. (See "Nutrition support in critically ill adult patients: Parenteral nutrition".)

•For patients with lower rates of chyle drainage, dietary modification may suffice to reduce the flow of chyle through the thoracic duct.

-A low-fat (<10 g/day), high-protein diet (oral or enteral) is undertaken to reduce intake of long-chain triglycerols.

-If pericardial drainage decreases, medium-chain triglycerols (MCTs) are added orally or enterally. MCTs are absorbed via intestinal cells and transported via the portal vein to the liver and thus bypass the thoracic duct.

-Patients at high risk of essential fatty acid deficiency are treated with peripheral intravenous fat emulsions (eg, 250 mL of 20 percent emulsion three times per week).

-For patients on a low-fat oral or enteral diet for 7 days with continued chyle drainage (>100 mL/day), we suggest switching to TPN.

•Octreotide – For patients with chylopericardium receiving a trial of medical therapy for chylopericardium, we suggest treatment with octreotide. The octreotide dose is 100 micrograms subcutaneously three times per day for two weeks [1]. Case reports have described successful treatment of postsurgical or malignancy-associated chylopericardium with off-label use of octreotide, a long-acting somatostatin analog [29,30]. The mechanism of action is presumed to be a reduction in chyle production and thoracic duct flow rate.

Surgical intervention — If pericardial drainage persists after 7 to 14 days of TPN or the pericardial effusion recurs, we suggest surgical treatment. This approach is based upon limited data from case series [2,25]. Significant nutritional loss is a factor favoring surgical intervention. Nonoperative therapy is usually unsuccessful when chylopericardium is secondary to congenital lymphangiomatosis.

Surgery typically consists of ligation of the thoracic duct and tributary lymphatics along with either pericardiotomy or pericardiectomy [25,31]. A common approach includes video-assisted thorascopic surgery (VATS) or thoracotomy and ligation of the thoracic duct (near the diaphragm), partial pericardiectomy, and creation of a pericardiopleural fistula (pericardial window) [32]. Recurrent chylopericardium after thoracic duct ligation and pericardial window creation is rare (<5 percent) [25,32].

For patients who are deemed to be at high risk for surgical complications, thoracic duct embolization has been proposed as a less invasive alternative [33,34].

CHOLESTEROL PERICARDITIS

Etiology of cholesterol pericarditis — Causes of cholesterol pericarditis include:

●Rheumatoid pericarditis [35-39]. (See "Pericardial involvement in systemic autoimmune diseases", section on 'Rheumatoid arthritis'.)

●Hypothyroidism [40]. (See "Diagnosis of and screening for hypothyroidism in nonpregnant adults".)

●Tuberculous pericarditis. (See "Tuberculous pericarditis".)

●Pericardial trauma. (See "Post-cardiac injury syndromes", section on 'Posttraumautic pericarditis'.)

However, many cases of cholesterol pericarditis are idiopathic.

The pathogenesis of cholesterol pericarditis has not been fully determined. Cholesterol generally remains in solution in an acute pericardial effusion. If the pericardial effusion is not relieved, lipoprotein degradation occurs over time, cholesterol is no longer dissolved and cholesterol crystals appear in the effusion and deposited in the pericardial tissue [20]. Histopathology demonstrates cholesterol crystals in pericardial tissue with a surrounding granulomatous foreign body reaction [39].

Clinical manifestations — The clinical manifestations of cholesterol pericarditis are those of acute or recurrent pericarditis and the underlying cause of pericardial disease.

●Clinical presentation – The major clinical manifestations of pericardial inflammation include pleuritic chest pain, pericardial friction rub, and electrocardiographic changes (eg, widespread ST elevation or PR depression). Some patients present with systemic symptoms such as fever, flu-like symptoms, and leukocytosis. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Clinical features'.)

In addition, some patients with cholesterol pericarditis present with dyspnea, elevated jugular venous pressure, pulsus paradoxus, and other signs of cardiac tamponade. (See "Cardiac tamponade".)

●Echocardiography – The standard initial test to identify a pericardial effusion and to evaluate for signs of cardiac tamponade is a transthoracic echocardiogram. The pericardial effusion with cholesterol pericarditis is often large, but moderate or small effusions have been described [39]. (See "Pericardial effusion: Approach to diagnosis", section on 'Echocardiography' and "Cardiac tamponade".)

●Other cardiac imaging – Imaging with cardiac CT or cardiovascular magnetic resonance (CMR) imaging is reserved for patients with nondiagnostic echocardiographic evaluation who require further assessment to identify and examine a pericardial effusion or to identify other suspected pericardial pathology (eg, constrictive pericarditis).

Pericardial thickening is more accurately assessed by cardiac CT or CMR imaging than by echocardiography. (See "Pericardial effusion: Approach to diagnosis", section on 'Cardiac CT and CMR'.)

Diagnosis of cholesterol pericarditis — As with other types of pericardial effusion, pericardial fluid sampling is required to make the diagnosis. (See "Pericardial effusion: Approach to diagnosis", section on 'Pericardial fluid analysis and biopsy'.)

Pericardial fluid findings include:

●The fluid is usually clear (although it occasionally may be cloudy or turbid) and is classically described as having a glittering gold paint appearance, although many other colors have been described [1,20].

●The concentration of cholesterol in the pericardial effusion usually equals or exceeds that of blood, often attaining values above 500 mg/dL (13 mmol/L).

●The fluid contains cholesterol crystals, foam cells, macrophages, and giant cells. Bleeding associated with inflammation is thought to be the source of cholesterol in the pericardial fluid, and evidence of current or previous hemorrhage is usually evident.

If pericardial tissue is obtained (eg, for biopsy in patients with suspected tuberculous pericarditis or as a specimen obtained during pericardiectomy), it shows a thickened pericardium with an inner surface lined with plaques and cholesterol deposits. Histologic findings include fibrosis, inflammatory cells, cholesterol clefts, crystals of variable geometry, and giant cell granulomata.

Differential diagnosis — The pericardial effusion associated with myxedema also may have a high cholesterol concentration, but crystals are usually absent. The distinction between most pericardial effusions associated with hypothyroidism and rare cases of cholesterol pericarditis with hypothyroidism is important since pericardial effusion associated with hypothyroidism without elevated cholesterol levels may resolve with thyroid hormone replacement therapy. (See "Clinical manifestations of hypothyroidism" and "Treatment of primary hypothyroidism in adults".)

As noted above, cholesterol pericarditis is distinguished from chylopericardium by differences in pericardial fluid findings. (See 'Differential diagnosis' above.)

Management

●Pericardial drainage – As noted above, initial pericardial fluid drainage is a component of the diagnosis and/or management of cholesterol pericarditis (algorithm 1). Following diagnostic or therapeutic pericardial fluid drainage, catheter drainage is continued until the volume of flow is <25 mL/day.

Patients with cardiac tamponade require urgent pericardial fluid drainage to alleviate symptoms and prevent hemodynamic collapse. (See "Cardiac tamponade", section on 'Management'.)

●Treatment of cause – All patients should receive treatment for the underlying cause of pericarditis. (See 'Etiology of cholesterol pericarditis' above.)

●Pericardiectomy – While pericardiocentesis provides short-term therapy, conservative therapy is rarely sufficient for long-term management of cholesterol pericarditis. Cholesterol effusions tend to recur with associated risk of cardiac tamponade, and the thickened scarred pericardium poses a long-term risk for development of constrictive pericarditis [1]. Most patients with cholesterol pericarditis require complete pericardiectomy [1,41]. (See "Recurrent pericarditis", section on 'Role of pericardiectomy'.)

•For patients with cholesterol pericarditis who present with cardiac tamponade, we suggest pericardiectomy.

•For patients with cholesterol pericarditis who do not present with tamponade, careful follow-up is indicated following pericardiocentesis to assess for recurrent pericardial effusion. If pericardial effusion recurs, we suggest pericardiectomy.

SUMMARY AND RECOMMENDATIONS

●Chylopericardium – Chylopericardium is a rare type of pericardial effusion comprised of chyle, the normal content of the lacteals (lymphatics of the small intestine) and the thoracic duct (figure 1). Chylopericardium may be primary (idiopathic) or secondary to injury to the thoracic duct (eg, iatrogenic, mediastinal neoplasm, central vein thrombosis, trauma). (See 'Etiology of chylopericardium' above.)

●Clinical presentation of chylopericardium – The clinical presentation of chylopericardium varies widely. Some patients present with symptoms and signs of acute pericarditis (including chest discomfort), some present with cardiac tamponade (with dyspnea and hypotension), some have chronic systemic illness, and some have no symptoms. (See 'Clinical manifestations' above.)

●Diagnosis of chylopericardium – The diagnosis of chylopericardium is confirmed by pericardial fluid analysis. The milky, opalescent pericardial fluid (picture 1) has a triglyceride level greater than 500 mg/dL (5.65 mmol/L), cholesterol/triglyceride ratio of less than 1, negative cultures and cytology, lymphocyte predominance, and fat globules. (See 'Diagnosis' above.)

●Management of chylopericardium (See 'Management' above.)

•Patients with cardiac tamponade require urgent pericardial fluid drainage to alleviate symptoms and prevent hemodynamic collapse. (See "Cardiac tamponade", section on 'Management'.)

•General measures for all patients include treatment of the underlying condition, fluid and electrolyte replacement, and nutritional intervention to reduce chyle flow (total parenteral nutrition [TPN] or low-fat, high-protein diet plus medium-chain triglycerols [MCTs]). (See 'General measures' above.)

For patients presenting with cardiac tamponade or >500 mL/day of chyle drainage, we suggest TPN (Grade 2C). The abrupt decline in chyle flow with TPN may prevent nutritional deficiencies and promote healing. (See "Nutrition support in critically ill adult patients: Parenteral nutrition".)

For patients with lower rates of chyle drainage, dietary modification may suffice to reduce the flow of chyle through the thoracic duct. For patients on a low-fat oral or enteral diet for seven days with continued chyle drainage (>100 mL/day), we suggest switching to TPN (Grade 2C).

•For most patients with chylopericardium, we suggest treatment with octreotide (Grade 2C). The octreotide dose is 100 microgram subcutaneously three times per day for two weeks. (See 'General measures' above.)

•If pericardial drainage persists after 7 to 14 days of TPN or the pericardial effusion recurs, we suggest surgical treatment (Grade 2C). Surgery typically consists of ligation of the thoracic duct and tributary lymphatics along with either pericardiotomy or pericardiectomy. (See 'Surgical intervention' above.)

●Cholesterol pericarditis – Cholesterol pericarditis is a rare complication of chronic pericardial inflammation and effusion and is thought to be exacerbated by cholesterol crystal deposition in the pericardium. Causes include rheumatoid pericarditis and hypothyroidism, though many cases are idiopathic. (See 'Etiology of chylopericardium' above.)

●Clinical presentation of cholesterol pericarditis – The clinical manifestations of cholesterol pericarditis are those of acute pericarditis (pleuritic chest pain, pericardial friction rub) and the underlying cause of pericardial disease. (See 'Clinical manifestations' above.)

●Diagnosis of cholesterol pericarditis – The pericardial fluid is usually clear (although it may be cloudy or turbid) and classically has a glittering gold paint appearance. The cholesterol concentration in the fluid usually equals or exceeds that of blood. The fluid contains cholesterol crystals, foam cells, macrophages, and giant cells. (See 'Diagnosis of cholesterol pericarditis' above.)

●Management of cholesterol pericarditis – All patients should receive treatment for the underlying cause of pericarditis. Most patients require complete pericardiectomy. (See "Recurrent pericarditis", section on 'Role of pericardiectomy'.)

•Cardiac tamponade – Patients with cardiac tamponade require urgent pericardiocentesis. In addition, once the patient is stabilized, we suggest pericardiectomy (Grade 2C).

•Patients without cardiac tamponade – For patients with cholesterol pericarditis not presenting with cardiac tamponade, careful follow-up is indicated after diagnostic pericardiocentesis. If pericardial effusion recurs, we suggest pericardiectomy (Grade 2C).