Cholesterol Pericarditis.

Cholesterol pericarditis is a rare condition characterized by a large, chronic cholesterol-rich pericardial effusion that often manifests with symptoms of heart failure. We report a case of an asymptomatic 51-year-old man with a massive cholesterol-rich pericardial effusion with echocardiographic evidence of impending tamponade. (Level of Difficulty: Advanced.).

Introduction

Cholesterol pericarditis is a rare entity with chronic, large, cholesterol-rich pericardial effusions. Although the pathophysiology of this accumulation is unclear, the sources of cholesterol are thought to be blood and associated inflammation. Cholesterol pericarditis has been associated with rheumatoid arthritis, hypothyroidism, and tuberculosis. However, many cases remain idiopathic. The diagnosis of cholesterol pericarditis is supported by pericardial fluid analysis with elevated cholesterol content (>70 mg/dL), cholesterol crystals under polarized light microscopy, or both. Classically, the pericardial fluid has a “gold paint” consistency, with the inner surface of the pericardium lined with cholesterol deposits. Cholesterol pericarditis may manifest as pericardial effusion, cardiac tamponade, or effusive-constrictive pericarditis. Here we describe a unique case of an asymptomatic patient with a chronic, massive, idiopathic, and recurrent cholesterol-rich pericardial effusion with echocardiographic findings suggestive of impending tamponade.

Learning Objectives

To make a differential diagnosis of the cause of a pericardial effusion with multimodality imaging and pericardial fluid analysis.

To understand the natural history of cholesterol pericarditis, including the frequent need for surgical management.

History of Presentation

A 51-year-old man with no medical history presented in August 2015 for lightheadedness. He had sustained blunt chest trauma 6 weeks earlier. He had mild chest discomfort, which resolved with time. Several weeks later, he felt lightheaded, and an echocardiogram revealed a large pericardial effusion. Pericardiocentesis was recommended, but the patient was hesitant to proceed. A repeat echocardiogram 2 months later was unchanged. Results of an evaluation for infectious, autoimmune, endocrine, and neoplastic causes were negative. He was asymptomatic and did not seek follow-up care.

In July 2021, the patient established primary care at our hospital. Although he was asymptomatic, his history prompted an echocardiogram, which revealed a massive pericardial effusion measuring 5.5 cm (Figures 1A to 1F, Videos 1, 2, 3, 4, and 5) with right atrial (RA) and right ventricular (RV) diastolic collapse, respiratory variation in tricuspid inflow velocities (∼50%), and inferior vena cava plethora. These findings raised concern for cardiac tamponade. His electrocardiogram (ECG) showed diminished voltages without electrical alternans (Figure 2A). The patient was admitted to the cardiac intensive care unit. Physical examination revealed elevated jugular venous pressure, distant heart sounds without friction rub, and clear lungs. Pulsus paradoxus was 12 mm Hg.

Figure 1

Transthoracic Echocardiogram

(A) Reversed apical 4-chamber view with pericardial effusion (asterisk) and right atrial collapse (arrow). (B) Parasternal long-axis view with right ventricular collapse (arrow). (C) Parasternal short-axis view with right ventricular collapse (arrow). (D) Plethoric inferior vena cava. (E and F) Tricuspid (significant respiratory variation; arrowheads mark inspiration) and mitral inflow velocities.

Figure 2

Electrocardiograms

(A) Pre-pericardiocentesis. (B) Post-pericardiocentesis.

Investigations

He underwent right-sided heart catheterization (Figures 3A to 3D, Table 1) and pericardiocentesis (Figures 4A and 4B). The opening peak and mean intrapericardial pressures were 11 and 8 mm Hg, respectively. Approximately 2 L of golden fluid (Figure 4C) was obtained. Postdrainage intrapericardial pressure was 3 mm Hg with negative inspiratory pressure. A pericardial drain was placed.

Figure 3

Right-Sided Heart Catheterization With Equal and Elevated Diastolic Pressures

(A) Right atrial (RA) pressure. (B) Right ventricular (RV) pressure. (C) Pulmonary artery (PA) pressure. (D) Pulmonary capillary wedge pressure (PCWP). Spo2 = peripheral oxygen saturation.

Table 1

Hemodynamic Measurements From Cardiac Catheterization

RA pressure, mm Hg	14
RV systolic pressure, mm Hg	32
RV diastolic pressure, mm Hg	15
PA systolic pressure, mm Hg	35
PA diastolic pressure, mm Hg	16
PCWP, mm Hg	16
Cardiac output, L/min	4.64
Cardiac index, L/min/m2	2.09
SVR, dynes/s/cm-5	789
PVR, dynes/s/cm-5	155
Predrainage intrapericardial pressure, mm Hg	11
Postdrainage intrapericardial pressure, mm Hg	3

PA = pulmonary artery; PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance; RA = right atrial; RV = right ventricular; SVR = systemic vascular resistance.

Figure 4

Pericardiocentesis

(A) Intrapericardial pressure pre-drainage. (B) Post-drainage. (C) Gold paint appearance. (D) Polarized light microscopy revealing cholesterol crystals (arrow) and foam macrophages (arrowhead). Spo2= peripheral oxygen saturation.

Results of a serologic work-up were negative (Table 2). Pericardial fluid analysis yielded a cholesterol concentration of 90 mg/dL (normal, 19.3-38.7 mg/dL), with normal values for other biomarkers (Table 3). Abundant cholesterol crystals and foam macrophages, containing an abundance of cholesterol, were seen on pericardial fluid microscopy (Figure 4D), thereby confirming cholesterol pericarditis.

Table 2

Serologic Testing

Blood Test	Serum Level (Reference Range)
COVID-19 antigen	Negative
White blood cells, k/cm2	8.0 (3.6-11.0)
Hemoglobin, g/dL	16.4 (13.6-17.4)
Platelets, k/cm2	214 (150-400)
Protein, g/dL	7.0 (6.4-8.5)
Albumin, g/dL	3.9 (3.4-5.5)
Blood urea nitrogen, mg/dL	9 (8-20)
Creatinine, mg/dL	0.9 (0.5-1.2)
Cholesterol, mg/dL	224 (135-200)
Triglycerides, mg/dL	189 (0-150)
Troponin I, ng/mL	0.00 (0.00-0.08)
D-dimer, ng/mL	392 (0-500)
High-sensitivity C-reactive protein, mg/L	1.85 (<10)
Erythrocyte sedimentation rate, mm/h	3 (0-20)
Antinuclear antibody	Negative
Rheumatoid factor, IU/mL	11 (0-13.9)
Anti–double-stranded DNA	Negative
Anti–cyclic citrullinated peptide immunoglobulin G, U/mL	<0.54
Thyroid-stimulating hormone, U/mL	1.90 (0.55-4.78)
QuantiFERON TB-Gold	Negative

Table 3

Pericardial Fluid Testing

Test	Fluid Level
Appearance	Turbid, yellow
Total nucleated cells, n/cm2	12,754
Red blood cell count, n/cm2	<1,000
Gram stain and culture	Negative
Acid-fast bacilli culture and stain	Negative
Lactate dehydrogenase, U/L	141
Cholesterol, mg/dL	90
Amylase, U/L	25
Triglycerides, mg/dL	15
Adenosine deaminase, U/L	4
Cytology	Negative

Management

Subsequently, the patient had pleuritic chest pain that was improved by leaning forward. ECG showed resolution of low voltage without signs of pericarditis (Figure 2B). A 90-day course of colchicine (1.2 mg twice and 0.6 mg twice daily thereafter) and ibuprofen (800 mg 3 times daily) was prescribed. Drain output was <50 mL/day 2 days later. Echocardiogram revealed no effusion. The pericardial drain was removed, his chest pain subsided, and he was discharged.

Follow-up echocardiogram 1 month later revealed a large effusion without tamponade. The patient remained asymptomatic. He was referred to cardiac surgery, and cardiac magnetic resonance (CMR) revealed a left ventricular (LV) end-diastolic volume index of 54 mL/m2 (normal, <84 mL/m2) with an LV ejection fraction of 59% (normal, 50%-75%). A simple, free-flowing, circumferential pericardial effusion measuring up to 3.8 cm in diameter was identified (Figures 5A to 5H, Video 6). No evidence of constrictive physiology or active pericardial or myocardial inflammation was present. He underwent repeat pericardiocentesis. Given his recurrent pericardial effusions, complete pericardiectomy occurred the following day, after which the patient has done well.

Figure 5

Cardiac Magnetic Resonance

(A and B) Long- and short-axis images; homogeneous pericardial effusion (white arrows), right atrial diastolic inversion (black arrow). (C and D) Long- and short-axis T2 maps without evidence of myocarditis. (E and F) Long- and short-axis images without inflammation in the myocardium, visceral (black arrows), and parietal (white arrows) pericardium. (G and H) Long- and short-axis phase-sensitive inversion recovery images without pericardial enhancement. LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

Discussion

This case illustrates an outcome of cholesterol pericarditis—a large asymptomatic effusion. Cholesterol pericarditis is a rare entity. Of several reported cases, most reported elevated pericardial cholesterol levels.,,5, 6, 7, 8 In this case, pericardial fluid had elevated cholesterol levels and cholesterol crystals with foam macrophages. These studies are not routine parts of a pericardial effusion analysis and were pursued because of the golden appearance of the pericardial fluid.

Many patients, including our own, did not present with chest discomfort, friction rub, or ECG signs of pericarditis.,,5, 6, 7, 8, 9 To our knowledge, this is the first report of cholesterol pericarditis with CMR findings, which revealed no active inflammation. It is unclear whether these patients would benefit from anti-inflammatory medications. Of note, the patient did receive several weeks of anti-inflammatory therapy before CMR evaluation. Other manifestations of cholesterol pericarditis include heart failure,,5, 6, 7, and, less commonly, shock.,

The chronic nature of these effusions makes determining the right time to intervene challenging. In this case, a massive effusion was present initially, but the patient was asymptomatic. Pericardiocentesis was pursued because of positive pulsus paradoxus and RA or RV diastolic inversion, findings concerning for a hemodynamically significant effusion. On recurrence of the effusion, the patient remained asymptomatic. It is unclear how long cholesterol effusions can be observed without definitive intervention, but this length of time is likely patient specific.

The pathogenesis of cholesterol pericarditis is incompletely understood. Hypothyroidism, and rheumatoid arthritis are commonly reported,,; however, several cases have been idiopathic. A potential cause in the case presented here is trauma before the index presentation, resulting in a post–cardiac injury syndrome. Blunt chest trauma is associated with chylous pericarditis, which has elevated cholesterol and triglyceride levels. Normal triglyceride levels favored the diagnosis of cholesterol over chylous pericarditis here.

Cholesterol effusions often reaccumulate,,, necessitating surgery, as was pursued here. Although clinical and imaging signs of constrictive physiology were absent in our patient, this condition should be excluded because of anecdotal reports of constriction.

Conclusions

Cholesterol pericarditis is rare, with an unclear pathogenesis. Effusions are typically voluminous and chronic. Cardiogenic shock is uncommon, whereas heart failure is more frequent. The absence of these features in our patient despite a large effusion speaks to his impressive hemodynamic and pericardial compensation. Extended follow-up of more patients with cholesterol pericarditis is required to quantify long-term outcomes.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.