Cardiovascular Involvement in Erdheim–Chester Disease

7019 Background: Erdheim–Chester disease (ECD), an inflammatory myeloid neoplasm, is an histiocytosis associated with multisystem infiltration. Cardiovascular involvement in ECD is under-diagnosed and associated with poor outcome. The targetable BRAFV600Emutation is present in up to 70% of all ECD. Methods: Retrospective study of 205 patients (pts) with ECD who had cardiac imaging (195 MRI, 10 CT when MRI was contraindicated). We identified the types of lesions (infiltration, tumor, and effusion), localization (pericardial, myocardial, valvular) and consequences on cardiac function (coronary stenosis, atrial wall dyskinesia, diastolic and systolic functions). Results: 141 (68.8%) pts were male. 30 (14.6%) had mixed histiocytosis (mainly ECD + langerhans cell histiocytosis). BRAF mutation ( BRAFm) was found in 112 (54.6%) cases, while 59 pts (28.8%) were Wild Type (WT) and 34 pts (7.6%) had unknown BRAF status. Among the 205 cardiac imaging, 101 (49.3%) were abnormal. Cardiac involvement was found in 93 pts (49%). Among these, 72 had an impairment of the right ventricular atrioventricular sulcus (74%), 65 of the right atrium (RA) enclosure (69%). Alteration of Tricuspid Annular Plane Systolic Excursion was found in 15% and correlated with the size of the tumor. Pericardial involvement (effusion, thickening or contrast enhancement) was found in 59 pts (29%). Among BRAFm pts, 75 (67%) had a heart abnormality while 37 (33%) had normal imaging; Among WT pts 14 (23.7%) showed heart abnormality, whereas 45 (76.3%) had normal imaging (RR 2.8 (CI: 1.8-4.5); p = 1.8*10-7). A RA tumor was present in 51 (45.5%) BRAFm but only 6 (10.2%) WT pts respectively (RR 4.5 (CI : 2.0-9.8); p = 7*10-6). BRAFm was also associated with aortic infiltration (RR 1.76 (CI: 1.2–2.5)) and pericardial involvement (RR 2.12 (CI: 1.1–3.9), p = 0.0017). Conclusions: Cardiac infiltration is frequent in ECD (49.3%), especially RA tumor. BRAFm is associated with RA, aortic and pericardial involvements.

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Cardiovascular Involvement, an Overlooked Feature of Erdheim-Chester Disease

Medicine ◽

10.1097/01.md.0000145368.17934.91 ◽

2004 ◽

Vol 83 (6) ◽

pp. 371-392 ◽

Cited By ~ 158

Author(s):

Julien Haroche ◽

Zahir Amoura ◽

Elisabeth Dion ◽

Bertrand Wechsler ◽

Nathalie Costedoat-Chalumeau ◽

...

Keyword(s):

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Erdheim Chester ◽

Chester Disease

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Cardiovascular involvement in Erdheim–Chester disease

International Journal of Cardiology ◽

10.1016/j.ijcard.2011.05.028 ◽

2012 ◽

Vol 154 (2) ◽

pp. e24-e26 ◽

Cited By ~ 10

Author(s):

Pier Giorgio Masci ◽

Virna Zampa ◽

Andrea Barison ◽

Massimo Lombardi

Keyword(s):

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Erdheim Chester ◽

Chester Disease

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High Serum VEGF Level in Erdheim-Chester Disease: Correlation with Cardiovascular Involvement and Response to Treatment

Blood ◽

10.1182/blood-2019-129984 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2324-2324

Author(s):

Anaïs Roeser ◽

Marine Bravetti ◽

Levi-Dan Azoulay ◽

Makoto Miyara ◽

Jean-François Emile ◽

...

Keyword(s):

Serum Level ◽

High Serum ◽

Receptor Expression ◽

Response To Treatment ◽

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Vegf Level ◽

Erdheim Chester ◽

Chester Disease

Context - Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by tissue infiltration of CD68 (+), CD1a (-) histiocytes in various organs. It has been classified as a myeloid neoplasia since the discovery of the RAS-RAF-MEK-ERK pathway alterations. Angiogenesis displays an important role in neoplastic and inflammatory process. Vascular Endothelial Growth Factor (VEGF) is a major proangiogenic factor. VEGF is expressed by many tumor cells, and was found to be expressed by Langerhans histiocytic cells. Mechanisms of cardiovascular involvement in ECD are still not clear, however we hypothesize that VEGF may contribute to the development of lesions of ECD. We further hypothesize that VEGF serum level could help distinguish different profiles of patients and study their response to treatment. Patients and Methods - We conducted a retrospective study in patients with ECD seen in the French National Reference Center for Histiocytoses of the Pitié-Salpêtrière Hospital. These patients had histologically confirmed ECD and were included in the study if they had at least one determination of serum VEGF. Serum VEGF level was assessed by ELISA and considered high when above a concentration of 500pg/mL. Evaluation of cardiac and vascular involvements was based on cardiac magnetic-resonance imaging and CT-angiography of the aorta as often as possible, and replaced by other imaging modalities when they were contraindicated. Results - We screened 254 patients of whom 231 had had at least one determination of VEGF serum level. Serums VEGF were high in 122 out of 231 patients (52.8%). Patients with a high serum VEGF level had more frequently a vascular involvement of ECD (68.8% vs 48.6%, p=0.001), especially signs of a "coated aorta" (47.5% vs 33%, p=0.025). Cardiac involvement was also more prevalent in patients with high serum VEGF level (59% vs 41.2%, p=0.007). Notably, coronary arteries were twice as frequently affected (28.7% vs 14.7%, p=0.010). BRAF status was not significantly different between patients with high or low levels of VEGF. VEGF level were not correlated to the presence of an inflammatory syndrome (evaluated on CRP elevation). At first determination, median serum VEGF among patients with high levels was 850pg/mL (SD 682.22). Under treatment, we observed a decrease of the serum VEGF level. Among 68 patients with a serum VEGF level determination at 12 months, the concentration of VEGF decreased significantly (mean difference 305.4, p<10-6), reaching a median of 507pg/mL (SD 552.58) at 12 months. Conclusion - Cardiovascular involvement is frequent and prognostically relevant in ECD. Evaluation of ECD clinical course and response to treatment is still challenging, and repeated imaging is often necessary. VEGF serum level could help distinguish patients with cardiovascular profile and contribute to follow up under treatment. Comprehension of the role of VEGF and the possible impact of anti-VEGF treatment will benefit from a study of VEGF and VEGF-receptor expression in lesions of ECD patients. Disclosures No relevant conflicts of interest to declare.

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Twelve Years of Follow-Up With Serial Cardiac Magnetic Resonance Scans in Erdheim-Chester Disease With Cardiovascular Involvement

Circulation Cardiovascular Imaging ◽

10.1161/circimaging.118.008808 ◽

2019 ◽

Vol 12 (3) ◽

Author(s):

Chrysanthos Grigoratos ◽

Antonio De Luca ◽

Nicola Martini ◽

Giovanni Donato Aquaro

Keyword(s):

Cardiac Magnetic Resonance ◽

Magnetic Resonance ◽

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Erdheim Chester ◽

Chester Disease

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Erdheim-Chester Disease With Cardiovascular Involvement and BRAF V600E Mutation

Circulation Journal ◽

10.1253/circj.cj-16-0109 ◽

2016 ◽

Vol 80 (7) ◽

pp. 1657-1659 ◽

Cited By ~ 1

Author(s):

Kenichi Okamura ◽

Yoshihiro Suematsu ◽

Sei Morizumi ◽

Mitsuhiro Kawata ◽

Yuichi Dai ◽

...

Keyword(s):

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Erdheim Chester ◽

Chester Disease

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Plasma Chromogranin A as a marker of cardiovascular involvement in Erdheim–Chester disease

OncoImmunology ◽

10.1080/2162402x.2016.1181244 ◽

2016 ◽

Vol 5 (7) ◽

pp. e1181244 ◽

Cited By ~ 9

Author(s):

Elisabetta Ferrero ◽

Angelo Corti ◽

Julien Haroche ◽

Daniela Belloni ◽

Barbara Colombo ◽

...

Keyword(s):

Chromogranin A ◽

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Erdheim Chester ◽

Chester Disease

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Multimodality imaging showing complete cardiovascular involvement by Erdheim–Chester disease

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ejechocard/jeq052 ◽

2010 ◽

Vol 11 (7) ◽

pp. E25-E25 ◽

Cited By ~ 9

Author(s):

Mohsen S. Alharthi ◽

Anna Calleja ◽

Prasad Panse ◽

Christopher Appleton ◽

Dawn E. Jaroszewski ◽

...

Keyword(s):

Multimodality Imaging ◽

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Erdheim Chester ◽

Chester Disease

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Erdheim-Chester disease presenting as a intracardiac mass and pericardial effusion confirmed by biopsy: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytab351 ◽

2021 ◽

Author(s):

Minjae Yoon ◽

Seung Hyun Lee ◽

Hyo Sup Shim ◽

Seok-Min Kang

Keyword(s):

Pericardial Effusion ◽

Median Sternotomy ◽

Braf V600e ◽

Right Atrial ◽

Intracardiac Mass ◽

Cardiac Wall ◽

Erdheim Chester Disease ◽

Cardiovascular Involvement ◽

Erdheim Chester ◽

Chester Disease

Abstract Background Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that can affect the bones, heart, lungs, brain, and other organs. Cardiovascular involvement is common in ECD and is associated with a poor prognosis. Here, we report a case of ECD presenting as a intracardiac mass and pericardial effusion confirmed by biopsy with sternotomy. Case summary A 54-year-old man was admitted because of dyspnoea. He was previously diagnosed with bilateral hydronephrosis and retroperitoneal fibrosis. Echocardiography revealed a large amount of pericardial effusion and echogenic mass on the right atrial (RA) side and atrioventricular (AV) groove. Cardiac magnetic resonance imaging and positron emission tomography-computed tomography (CT) revealed infiltrative mass-like lesions in the RA and AV groove. Pericardial window formation and pericardial biopsy were performed, and the pathologic results showed only pericardial fibrosis with no specific findings. Bone scan revealed increased uptake in the long bones. Considering the high probability of ECD based on the patient’s manifestations and the imaging findings, we performed a cardiac biopsy with median sternotomy despite initial insufficient pathologic results in the pericardial biopsy. The surgical findings included multiple irregular and firm masses on the cardiac wall and large vessels; after obtaining a large amount of suspicious mass, ECD accompanied with CD68 (+) and BRAF V600E mutation was confirmed. Discussion ECD can be associated with various forms of cardiovascular involvement. Considering the multi-systemic manifestations and difficulty in identifying this rare disease, a comprehensive and meticulous diagnostic work-up is crucial.

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