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Introduction

Idiopathic chylopericardium (CP) is a rare clinical entity that was first reported by Hasebroek in 1888 (1). The term primary CP was initially used in a study by Groves and Effler in 1954 (2), which described a case of isolated accumulation of chyle in the pericardium without any evident cause. Secondary CP typically refers to complications due to cardiothoracic surgery, trauma or a thrombus in the jugular vein, infection, radiotherapy, mediastinal tumors, hygromas, bone lymphangiomas, lymphoma, acute necrotic pancreatitis and other malignancies (3–5). Dib et al (6) analyzed the CP cases reported in the literature between 1996 and 2006, and observed that the idiopathic cause of CP accounted for 56% of cases. The possible mechanisms of idiopathic CP include the following: i) Impaired lymphatic valves on branches that are connected to the thoracic duct and pericardium lymphatic vessel; ii) elevated pressure in the thoracic duct that may occur in lymphangiectasia; iii) abnormal communication of lymphatic vessels to the pericardial lymphatics resulting in chylous reflux; and iv) congenital malformation.

Generalized lymphatic anomaly (GLA) is a rare congenital disease resulting in malformation of lymphatic vessels. GLA is known by multiple terms, including lymphangiomatosis, generalized lymphangioma, systemic cystic angiomatosis, multiple lymphangiectasia and generalized lymphatic malformation (7,8). Lymphatic anomalies are considered to arise from disordered lymphatic development resulting in the proliferation of lymphatic channels (8). Lymphatic anomalies can also cause chylopericardium (CP), which is very rare. In the present case, lymphatic abnormality was confirmed by lymphangiography and surgery.

The present study reports a case of CP in an Asian male patient, who presented with no specific symptoms and with occasional detection of pericardial effusion by ultrasound. Furthermore, a literature review was performed to improve the understanding on the diagnosis and treatment of primary CP.

Case report

In June 2008, a 57-year-old man was admitted to the Cardiology Care Unit of Beijing Hospital (Beijing, China) with symptoms of dyspnea and chronic cough that persisted for 10 months. The patient did not present fever or chills at home. Workup examination included transthoracic echocardiography, which was performed 2 months prior to this admission, which demonstrated a large cardiac effusion. Upon physical examination on admission, the blood pressure was 135/80 mmHg and the pulse was at 95 bpm. The patient was alert and oriented, and a neck exam did not detect jugular venous distention (JVD). The lungs were clear upon bilateral auscultation, without wheezing or crackles. Cardiovascular examination demonstrated a regular heart rhythm without murmurs, and the heart sound was distant. His abdomen was soft and non-tender on palpation, and the patient did not present hepatosplenomegaly. A chest X-ray scan demonstrated an enlarged cardiac silhouette, as shown in Fig. 1. Transthoracic echocardiography was repeated and demonstrated a large cardiac effusion with 6–34 mm of fluid in the apex and basal area (Fig. 2). Laboratory testing revealed an erythrocyte sedimentation rate of 12 mm/h (normal range, <15 mm/h). A purified protein derivative skin test was negative.

Figure 1. Chest X-ray scan demonstrated cardiomegaly with normal pulmonary vasculature.

Figure 2. Apical four-chamber view on echocardiography demonstrated large pericardial effusion (depth, 3.46 cm).

To alleviate the symptom of dyspnea and clarify the reason for it, the patient underwent diagnostic and therapeutic pericardiocentesis with the removal of 3,080 ml milky fluid with symptomatic relief (Fig. 3). The pericardial effusion was confirmed to be chylous with the following contents: Specific gravity ≥1.030; red blood cell count, 2,880/mm3; white blood cell count, 350/mm3; monocytes, 90%; neutrophils, 10%; glucose, 7 mmol/l; total protein, 82 g/l; albumin, 27 g/l; lactate dehydrogenase, 150 U/l; triglycerides (TG), 13.4 mmol/l; total cholesterol (TC), 3.4 mmol/l. The pericardial effusion was negative for tuberculosis via polymerase chain reaction analysis, while bacterial culture was also negative. Lymphangioscintigraphy with 99mTc-DX demonstrated obstruction of the upper part of the thoracic duct and abnormal accumulation of radiotracer was observed in the pericardium after 3 h of injection (Fig. 4).

Figure 3. Pink milky pericardial effusion obtained through drainage during pericardiocentesis.

Figure 4. Lymphoscintigraphy revealing the obstruction of the upper thoracic duct, and abnormal accumulation of radiotracer was observed in the pericardium after 3 h of injection.

The patient was subsequently transferred to the Beijing Shijitan Hospital (Beijing, China) for surgery. Lymphangiography was conducted prior to surgery, which revealed four lymphatic collaterals below the left sternoclavicular joint divided from the thoracic duct. These collaterals communicated with the left supraclavicular vein, cervical lymph nodes and right supraclavicular vessel. Certain other communicating braches from the thoracic duct were connected with the left bronchomediastinal trunks abutting the pericardial sac. Chylous regurgitation was observed from the thoracic duct toward the left bronchomediastinal trunks. The patient was identified to have congenital anomalies of the thoracic duct. The end of thoracic duct was not converged to the left subclavian vein as usual, but branched with multiple small vessels and connected with other lymphatic vessels. Thus, the patient underwent thoracic duct-left internal jugular vein anastomosis and ligation of communicating branches between the thoracic duct and left bronchomediastinal trucks.

At 1 month after surgery, follow-up echocardiography revealed recurrence of a pericardial effusion. The patient underwent further pericardiocentesis with removal of 200 ml chylous fluid, and conservative treatment including low-fat diet and medium-chain triglyceride (MCT) diet was continued from last admission. The patient responded well to treatment and presented a good quality of life without dyspnea on exertion upon follow-up at 6 months and 7 years.

Discussion

The pericardial space usually contains 25–35 ml of fluid, which is identical to lymph and is produced by the epicardium (9). The pericardium itself does not produce a large amount of fluid. Lymphatic vessels of the heart drain the pericardial fluid into the left subclavian vein via the mediastinal lymph vessels, lymph nodes and the thoracic duct (10). The main lymphatic flow from the pleura, the lower portion of the left lung, and the entire right lung and pericardium meet at the bronchomediastinal lymphatics (11,12). Therefore, lymphatic flow regurgitation can occur simultaneously in multiple sites in the thoracic cavity, such as the pleura, lungs and pericardium. Obstruction of the upper area of the thoracic duct may then cause CP, pulmonary lymphedema and chylothorax. Furthermore, the intestinal lymph will be affected by the obstruction and result in chylous ascites.

Primary CP is a rare clinical entity in which chylous fluid containing high concentrations of TG accumulate in the pericardial cavity. Causes of CP include congenital mediastinal lymphangiectasia, iatrogenic development following cardiac surgery, malignant tumors, blunt or penetrating trauma, infection and congenital lymphatic anomalies (6,11,13–15). It has been reported that ~56% of cases are idiopathic (6), and only ~100 CP cases have been reported worldwide (16). In the present study, a systematic review of the literature was performed to analyze the etiology, symptoms, physical examination features, laboratory findings, imaging, type of surgery and follow-up data of primary CP cases. A relatively large number of cases reported within the past 60 years were included in this systematic review. The current study aimed to provide further evidence for the recognition of primary CP.

A systematic PubMed (www.ncbi.nlm.nih.gov/pubmed) and Wanfang (www.wanfangdata.com.cn) database search was conducted in order to identify English and Chinese studies describing primary or idiopathic CP reported between January 1, 1950 and December 31, 2015. The search terms included the following: ‘primary chylopericardium’ or ‘idiopathic chylopericardium’. The bibliographies of all articles were subsequently independently reviewed by two of the authors. A total of 104 cases were identified from 92 studies (2–5,7,11–87). Patient demographics, clinical presentation, diagnosis and treatment were analyzed. Patients lacking laboratory data (such as the TG concentration), imaging or surgical findings that supported their primary or idiopathic CP definitive diagnosis were excluded from the present study. The mean ± standard deviation was used to express count variables, which were statistically analyzed by SPSS version 20 (IBM Corp., Armonk, NY, USA).

According to the literature review conducted in the present study, 53 male (50.96%) and 51 female (49.03%) CP patients were identified. The age at diagnosis ranged between 6 weeks and 79 years, with a mean 27.95±16.50 years, while 5 cases were <3 years old. The time from onset of symptoms to the diagnosis demonstrated a wide variation, ranging between a few hours and several years.

The clinical manifestations, physical examination features, electrocardiogram and X-ray finding are listed in Table I. Dyspnea was the most common initial presenting symptom, followed by coughing. Other symptoms included palpitation, chest pain, gastrointestinal (GI) symptoms, syncope, fatigue and edema. In addition, cardiac tamponade occurred in certain patients as a result of decreased cardiac output due to their chronic pericardial effusion. In the present review, approximately 39.42% of patients had no symptoms, although X-ray plain film demonstrated an enlarged cardiac silhouette. Signs of pericardial effusion were also identified during physical examination, including enlarged heart border, distant heart sounds, JVD and edema. JVD and a distant heart sound were only identified in <50% of the included cases. Furthermore, 16 cases presented with low voltage in the limb lead upon electrocardiographic examination. Cardiomegaly was easily identified by X-ray screening in 93.27% of cases.

Table I. Clinical data of 104 chylopericardium cases identified in the literature.

Table I.

Clinical data of 104 chylopericardium cases identified in the literature.

Characteristics	Number of cases (n)	Percentage (%)
Symptom
Asymptomatic	41	39.42
Dyspnea	48	53.90
Coughing	11	10.58
Palpitation	10	9.62
Cardiac tamponade	7	6.73
Chest pain	4	3.85
GI symptoms	4	3.85
Syncope	3	3.40
Fatigue	3	2.88
Edema	2	1.92
Physical examination
JVD	23	22.12
Distant heart sound	34	32.69
Electrocardiogram
Low voltage in limb lead	16	15.38
X-ray scanning
Cardiomegaly	97	93.27

[i] GI, gastrointestinal; JVD, jugular venous distention.

The diagnosis of chylous pericardium relied upon the pericardial fluid analysis. Regarding the appearance of the fluid, a milky white pericardial effusion (78 cases, 72.89%) was typically observed, followed by pink or bloody fluid (4 cases, 3.85%). The level of TG was tested in 63 cases and was in the range of 181–4299 mg/dl, with a median of 1305.43±865.34 mg/dl, while the TC level was tested in 42 cases and was within the range of 42–1021 mg/dl, with a mean value of 132.42±148.22 mg/dl. The TC/TG ratio in all CP patients included in the current study was <1.

Imaging served an important role in the exploration of the leak site of CP, as shown in Table II. In total, 42 (40.38%) cases underwent lymphangioscintigraphy and 24 of these cases presented abnormal accumulation within the pericardial sac. In addition, 24 cases (23.07%) underwent lymphangiography and 18 of them had abnormal finding; 35 (33.65%) cases underwent chest contrast-enhanced computed tomography (CT) scanning without any secondary disease finding.

Table II. Imaging data.

Table II.

Imaging data.

Type of imaging	Number of cases (n)	Percentage (%)	Abnormal finding (n)
Chest X-ray	97	93.27	97
Echocardiography	79	75.96	79
Lymphangioscintigraphy	42	40.38	24
Lymphangiography	24	23.07	18
Computed tomography	35	33.65	0

Of the 104 identified cases, treatment information was provided for 102 patients. A total of 62 cases were subjected to initial conservative management, including dietary control involving total parenteral nutrition (TPN), low-fat diet and MCT diet. Among these patients, 36 cases did not improve and underwent subsequent surgery, while 26 cases were successfully treated following conservative management. In total, 71 cases (71.2%) were treated by surgery. Formation of a pericardial window was used in 50 cases (48.08%) and ligation of the thoracic duct was performed in 46 cases (44.23%). There were also 4 cases (3.85%) that received embolization. Embolization of the thoracic duct was an uncommon type of surgery for CP, which was performed in weak patients or subsequent to failure of ligation. Furthermore, pericardioperitoneal shunt was conducted in 3 cases (3.88%). Only 1 case underwent reconstruction of the thoracic duct, which is rarely performed.

Follow-up data were recorded in 64 cases, with a median follow-up time of 12 months (1 month to 9 years) and all patients had a positive outcome. Only 1 case was complicated by constrictive pericarditis. No patients succumbed to the condition during the follow-up period.

A scoring system has been suggested by Dib et al (6) to assist in establishing the diagnosis of CP. The score is calculated according to the following features: i) Milky yellowish appearance of fluid; ii) TG level of >500 mg/dl; iii) TC/TG ratio of <1; and iv) negative fluid bacterial culture and lymphocytic predominance on fluid cell count. Each feature is given 1 point, and a score of 2 (specificity and sensitivity of 100%) is required for the diagnosis of CP (6). The patient in the current study had a score of 4, which could be confirmed as CP.

Other conditions that may mimic a chylous pericardium include cholesterol pericarditis (88,89) and purulent pericarditis (90,91), which can be complicated by a pericardial effusion with a positive chylous test. The pericardial effusion in cholesterol pericarditis typically appears orange and full of cholesterol crystals. Clinically, patients with purulent pericarditis typically have more severe presentation compared with patients with CP. Diagnosis of pericardial effusion secondary to cholesterol and purulent pericarditis depends on the cell count, biochemistry, cytology and fluid culture findings.

Echocardiography is helpful in diagnosing pericardial effusion and helps guide pericardiocentesis. Enlarged cardiac silhouette is often observed on chest X-ray scans in patients with CP (14). The main diagnostic methods for CP include lymphoscintigraphy and lymphangiography. However, diagnosis is highly variable depending on the device and technique. Lymphangiography is performed to assess the thoracic duct anatomy by administering a contrast agent directly into catheterized lymph vessels (20). When successful, this test is able to demonstrate the connection between the pericardial capacity and lymphatic system. However, lymphangiography is invasive and requires insertion of a catheter into a lymphatic vessel and use of a contrast agent. Combining lymphangiography and CT has also been reported to be useful for detecting lymphatic vessels and abnormal communications within the pericardial space (92). Lymphoscintigraphy is a noninvasive alternative to lymphangiography, which utilizes radionuclides as imaging agents and can be performed using oral or subcutaneous administration of radiotracers (93). Chest CT scanning is also helpful to detect the association between the thoracic duct and surrounding organs (94).

Regardless of the etiology of CP, conservative therapy in the absence of hemodynamic compromise is the first line treatment. MCT diet or TPN can also be attempted; however, the majority of patients will require pericardiocentesis for symptom alleviation (95). Pericardiocentesis followed by drainage and MCT diet should be considered as a primary management strategy since the mortality rate of CP is not high (6). Definitive treatment with surgery is recommended in cases where the daily pericardial drainage is at >1,500 ml/day, drainage does not decrease after 5 days (>500 ml/day) or malnutrition occurs (96). Management with pericardiocentesis alone rarely prevents recurrence. Pericardiocentesis followed by pericardiostomy s another reasonable approach, particularly when the patient is reluctant to undergo surgery or has a concomitant life-limiting disease. Conservative treatment failed in 57.1% of the cases as reported previously (1), and in 58.06% of cases as reported in the present study. However, surgical treatment was curative in all cases. For patients presenting a recurrent chylous pericardial effusion within 3-month, surgical treatment is recommended.

There are different approaches for the surgical treatment of CP (6). Pericardiectomy is performed to ensure complete drainage and to prevent secondary constrictive pericarditis. Creation of a pericardial window alone is insufficient since it has a high recurrence rate, as it does not close the communication between the thoracic duct and the pericardial sac (11). Ligation of the thoracic duct above the level of the diaphragm is the best choice and is recommended by the majority of surgeons (81). Video-assisted thoracoscopic surgery is also becoming more favorable by cardiothoracic surgeons since it is less invasive and affects the pulmonary function to a lesser extent. Furthermore, embolism of the thoracic duct is used in certain situation, and is an alternative type of surgery, particularly for patients who refuse to be subjected or re-subjected to more invasive surgery, or those that cannot tolerate anesthetization (10). Another novel surgical therapy is the reconstruction of the occluded thoracic duct (97). This approach is most consistent with the restoration of nearly normal physiology. Although thoracic duct reconstruction results in substantial symptomatic improvement and volume reduction, CP may recur. Recurrences should be managed conservatively since full restoration of the normal lymphatic flow may require a certain time.

The patient in the present case study underwent thoracic duct reconstruction surgery and required several months for complete restoration. However, the short term and long term prognosis of this patient was good. Based on the literature review conducted, the current case is the first reported case of primary CP that underwent lymphatic reconstructive surgery and had a 7-year follow up. This case aims to provide further insight on this condition to assist in the treatment of primary CP.

In conclusion, the present study reported the case of a 57-year-old Chinese male who presented with nonspecific symptoms of primary CP, which is a rare condition with only ~100 cases reported worldwide to date. The current patient underwent a rare type of surgery of the thoracic duct, namely left internal jugular vein anastomosis, which was only reported by Melduni et al from the Mayo clinic in 2008 (97). In addition, long-term follow-up findings subsequent to thoracic duct anastomosis surgery were reported for the present patient. A systematic literature review was also performed, analyzing the etiology, symptoms, physical examination findings, laboratory results, imaging, type of surgery and follow-up data of primary CP. A relative large number of cases reported during the past 60 years were included in this systematic review. Correct diagnosis can be achieved with analysis of the pericardial effusion, while lymphoscintigraphy and lymphangiography are useful for locating the chyle leak site. Surgical management is the most successful treatment and is associated with a favorable prognosis. The current study provided an overall perspective on the etiology, symptoms, physical examination and laboratory findings, imaging, type of surgery and follow-up data of primary CP, and this evidence will assist in improving the understanding and recognition of this rare disease.

References