Eosinophilic Endomyocardial Disease Research Articles

In-Depth Review of Loeffler Endocarditis: What Have We Learned?

Loeffler endocarditis, eosinophilic endocarditis or eosinophilic endomyocardial disease are conditions associated with hypereosinophilia and they affect the heart function. Loeffler endocarditis is a rare endomyocardial disorder thought to be caused by eosinophilic damage. The disorder is characterized by inflammatory infiltration, formation of thrombus within cardiovascular system, and ultimately fibrosis of the afflicted area. It can lead to multiple severe complications, including thromboembolic disease, thickening of fibrous tissue in the endocardium of ventricles, valve involvement, apical obliteration, and various heart disorders. Although early clinical intervention can lead to remission, the underlying mechanisms of the disorder remain unresolved. In the present article, we summarise the existing literature concerning Loeffler endocarditis based on PubMed, Web of Science, and other medical databases to conduct an in-depth review of the epidemiology, etiology, pathophysiological mechanisms, staging, diagnosis, treatment and prognosis of Loeffler endocarditis. Meanwhile, we provide novel patients data and clinical figures of Loeffler endocarditis to supplement the understanding of this cardiac disorder. The findings presented in this article provide a basis for further studies and can be used to improve management of the disorder.

Hypereosinophilic syndrome mimicking acute coronary syndrome

Hypereosinophilic syndrome (HES) is a heterogeneous group of disorders with peripheral blood hypereosinophilia and eosinophil-mediated organ involvement. It may be primary, secondary, or idiopathic. In very rare cases, HES can be familial occurring as an autosomal dominant disorder. Cardiac involvement usually presents as heart failure, intracardiac thrombus, arrhythmias, and rarely as acute coronary syndrome (ACS) and is a major cause of morbidity and mortality. Cardiac magnetic resonance imaging has emerged as a diagnostic modality in diagnosis of eosinophilic endomyocardial disease. We report a case of a young male with familial HES presenting as ACS and discuss diagnostic and therapeutic clinical management.

Development of eosinophilic endomyocardial disease in a patient with episodic angioedema and eosinophilia

Development of eosinophilic endomyocardial disease in a patient with episodic angioedema and eosinophilia

Eosinophilic endocardiomyopathy: a case presentation

Eosinophilic endocardiomyopathy is a major cause of morbidity and mortality among patients with hypereosinophilic syndrome (HES), a group of disorders characterized by the sustained overproduction of eosinophils, where eosinophilic infiltration causes the damage to multiple organs. We present the case of a 63-year-old man who had been investigated at the out-patient clinic for malaise, effort intolerance, dry cough and cognitive disturbances six months before his presentation to our hospital. He had been diagnosed with hypereosinophilia (51.14 x 10^9/L) and leukocytosis (69.7 x 10^9/L). Bone marrow biopsy resulted negative for abnormal myeloid maturation or lymphoproductive disorder. A brain magnetic resonance confirmed postischemic lesions and gastroscopy revealed esophageal varices grade I. According to immunologist's recommendation, who previously excluded systemic autoimmune disease, the patient was referred to our Cardiology Clinic for further investigations. The transthoracic echocardiography showed a dilated cardiomyopathy with global hypokinesia and ejection fraction of 40%. A multi-slice computer tomography coronarography (MSCT) excluded the presence of coronary artery disease. Cardiac magnetic resonance imaging demonstrated biventricular enlargement and global hypokinesia (trueFISP cine), myocardial oedema in the mid-cavity and in the apical segments (T2 STIR), diffuse endocardial late gadolinium enhancement of the left ventricular mid-cavity and apical segments and of almost the entire right ventricle (true FISP PSIR) indicating fibrosis/necrosis. Thrombi at both ventricular apices were also identified. These findings present the final stage in the time course of eosinophilic endomyocardial disease. The patient was dismissed with anticoagulation and immunosuppressive therapy. Two months later the patient was feeling better and the eosinophil counts significantly decreased. Eosinophilic endocardiomyopathy is characterized by three stages: an acute necrotic stage significant for direct endomyocardial infiltration and damage, an intermediate phase, in which thrombi form along the damaged endocardium and a fibrotic stage characterized by endomyocardial fibrosis. Cardiac magnetic resonance imaging is an important non-invasive tool for detection of all stages of eosinophil-mediated heart damage.

Gadolinium-enhanced cardiovascular magnetic resonance for the detection and characterization of Loeffler endocarditis in patients with hypereosinophilic syndrome

Hypereosinophilic syndrome (HES) is a rare disorder characterized by a marked and persistent peripheral blood eosinophilia combined with organ-system dysfunction caused by eosinophil-associated tissue damage [ 1 Chusid M.J. Dale D.C. West B.C. Wolff S.M. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). 1975; 54: 1-27 Crossref PubMed Scopus (1183) Google Scholar , 2 Klion A.D. Bochner B.S. Gleich G.J. et al. The Hypereosinophilic Syndromes Working G. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol. 2006; 117 (Epub 2006 May 3.): 1292-1302 Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar ]. The clinical manifestations of HES are variable and depend on the target-organ affection by eosinophils. Cardiac involvement, originally described by Loeffler [ [3] Löffler W. Endocarditis parietalis fibroplastica mit Bluteosinophilie. Ein eigenartiges Krankheitsbild. Schweiz Med Wochenschr. 1936; 66: 817-820 Google Scholar ], is frequent and cardiac dysfunction is the major cause of morbidity and mortality in HES-patients [ [4] Weller P.F. Bubley G.J. The idiopathic hypereosinophilic syndrome. Blood. 1994; 83: 2759-2779 PubMed Google Scholar ]. The cardiac pathology of HES has been temporally divided into three stages: early acute necrotic, then thrombotic, and finally a late fibrotic stage [ [4] Weller P.F. Bubley G.J. The idiopathic hypereosinophilic syndrome. Blood. 1994; 83: 2759-2779 PubMed Google Scholar ]. The diagnosis of eosinophilic cardiac disease is based on the co-existence of endomyocardial eosinophils on myocardial biopsy and cardiovascular abnormalities for which other possible causes have been excluded. However, biopsy is invasive and most standard non-invasive diagnostic tools such as echocardiography are often unsatisfactory in detecting cardiac involvement. Contrast-enhanced cardiovascular magnetic resonance imaging (CE-CMR) can characterize different myocardial tissue abnormalities by typical patterns of late gadolinium enhancement (LGE), including necrosis, inflammation, and fibrosis [ [5] Pennell D.J. Cardiovascular magnetic resonance. Circulation. 2010; 121: 692-705 Crossref PubMed Scopus (211) Google Scholar ]. Thus, CE-CMR is an attractive technique to directly visualize the various cardiac pathologies that occur during the different stages of Loeffler endocarditis. So far, the usage of CMR in diagnosing HES associated heart disease has been described only in single case reports [ 6 Puvaneswary M. Joshua F. Ratnarajah S. Idiopathic hypereosinophilic syndrome: magnetic resonance imaging findings in endomyocardial fibrosis. Australas Radiol. 2001; 45: 524-527 Crossref PubMed Scopus (25) Google Scholar , 7 Syed I.S. Martinez M.W. Feng D.L. Glockner J.F. Cardiac magnetic resonance imaging of eosinophilic endomyocardial disease. Int J Cardiol. 2008; 126 (Epub 2007): e50-e52 Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar , 8 Cheung S.C. Chan C.W. Insights of prognostication of Davies disease: what could we learn from serial magnetic resonance imaging studies?. Int J Cardiol. 2009; 12: 12 Google Scholar , 9 Chang S.A. Kim H.K. Park E.A. Kim Y.J. Sohn D.W. Images in cardiovascular medicine. Loeffler endocarditis mimicking apical hypertrophic cardiomyopathy. Circulation. 2009; 120: 82-85 Crossref PubMed Scopus (13) Google Scholar , 10 Deb K. Djavidani B. Buchner S. et al. Time course of eosinophilic myocarditis visualized by CMR. J Cardiovasc Magn Reson. 2008; 10: 21 Crossref PubMed Scopus (55) Google Scholar ] but no systematic evaluation has been reported. The purpose of this study was to evaluate the presence of cardiac involvement in patients with HES using CMR.

Eosinophil Granule Protein Localization in Eosinophilic Endomyocardial Disease

In this case report, eosinophilic endomyocardial disease was diagnosed in a patient on the basis of immunohistochemical evidence of eosinophil granule protein deposition in the heart, even in the absence of eosinophilic infiltration on cardiac biopsy.

Loeffler endocarditis: What have we learned?

Loeffler endocarditis, eosinophilic endomyocardial disease or fibroplastic endocarditis appears to be a subcategory of the Hypereosinophilic syndrome in which the heart is predominantly involved. It is an uncommon myocardial disease, thought to be secondary to eosinophils damage, characterized by fibrous thickening of the endocardium of one or both ventricles, leading to apical obliteration and multiple cardiovascular complications. Despite all the efforts, the ultimate responsible mechanisms of this entity remain unresolved. Many theories have been raised trying to explain this phenomenon, but nowadays the enigma in relation to the different patterns of evolution continues. In this concise review we discuss the different pathophysiologic theories postulated and the management of the cardiovascular complications. Perhaps it will serve to assist in recognition of patients with the same condition around the world.

Cardiac magnetic resonance imaging of eosinophilic endomyocardial disease

Idiopathic hypereosinophilic syndrome (HES) is rare and frequently involves the heart with development of endomyocardial fibrosis, a characteristic restrictive cardiomyopathy. Non-invasive diagnosis is frequently challenging. Recent developments in cardiac magnetic resonance (CMR) imaging techniques offer potential for improved detection and characterization of this entity. We describe the use of contrast-enhanced CMR to demonstrate thrombus, endomyocardial fibrosis and inflammation in eosinophilic endomyocardial disease. A three-layered appearance consisting of normal myocardium, thickened fibrotic endocardium with inflammatory exudate, and overlying thrombus was seen on cine-images. Post-contrast perfusion and delayed enhancement images confirmed the presence and location of endomyocardial fibrosis and thrombus. CMR is an important and powerful addition to current non-invasive diagnostic tools for the clinical diagnosis of eosinophilic endomyocardial disease, and may potentially obviate the need for cardiac biopsy in the future.

FIP1L1–PDGFRA positive chronic eosinophilic leukemia in Tunisian patients

Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion in HES supports the diagnosis of chronic eosinophilic leukemia (CEL) and provides a molecular explanation for the pathogenesis of this disorder. We screened seven Tunisian patients fulfilling the WHO criteria of HES for the presence of the FIP1L1-PDGFRA fusion gene using nested reverse transcription polymerase chain reaction on peripheral blood samples. Four of the seven patients were positive for this fusion gene. Sequence analysis revealed a substantial heterogeneity of the fusion transcripts due to the involvement of several FIP1L1 exons. All patients were male. The median age at diagnosis was 24 years (range, 18-50); one patient had a history of hypereosinophilia of more than 10 years. Two patients had clinically important and symptomatic eosinophilic endomyocardial disease with thrombotic events. Splenomegaly was constant in FIP1L1-PDGFRA positive CEL but not in the other HES patients (only 1/3).

Atypical Presentation of Eosinophilic Endomyocardial Disease

Idiopathic hypereosinophllic syndrome is classically defined as prolonged, unexplained peripheral eosinophilia in a patient presenting with evidence of end-organ damage. The heart is frequently Involved, resulting In eosinophilic endomyocardial disease and eventually restrictive cardlomyopathy. The mortality rate is high because of progressive heart failure or ventricular arrhythmias. We describe a patient who presented with a left ventricular apical thrombus without notable peripheral eosinophilia. Findings from clinical evaluation and extensive diagnostic testing, including right ventricular biopsy, were Inconclusive. Resection of the thrombus and subjacent endomyocardium revealed eosinophilic Infiltration of the endomyocardium, which led to the diagnosis of eosinophilic endomyocardial disease. Clinicians should be aware of the variable presentation of patients with eosinophil-associated endomyocardial disease so that affected patients may benefit from early diagnosis and treatment.

Coronary and Valve Angiodysplasia Unmasked by Eosinophilic Vasculitis and Endomyocarditis

A previously unreported case of a complex congenital cardiac anomaly consisting of coronary and valvular angiodysplasia, complicated by an eosinophilic endomyocardial disease, is described. The disorder presented clinically with congestive heart failure, which was characterized by evidence of floating masses causing severe pulmonary stenosis and dysfunction of the mitral and aortic valves. Symptoms of cardiac failure disappeared following pulmonary valve replacement and steroid therapy.

Severe mitral regurgitation in acute eosinophilic endomyocarditis: repair or replacement?

Established eosinophilic endomyocardial disease usually causes progressive heart failure from diastolic restriction and/or valvular dysfunction. Surgical treatment typically involves resection of endoventricular fibrosis and atrioventricular valve replacement. However, little is known of the clinicopathological behaviour and perioperative course of this disease in the early stages. Mitral valve repair seemingly offers an attractive surgical option in this scenario as it avoids prosthetic thrombosis--a recognized late complication of this disease. This was attempted in conjunction with left ventricular thrombectomy in a patient with acute hypereosinophilia and congestive heart failure associated with severe mitral regurgitation and restrictive cardiomyopathy. Although the early clinical and echocardiographic outcome was excellent, the patient deteriorated rapidly after 3 months when identical pathology relapsed in the left heart causing recurrent severe mitral regurgitation and heart failure. Cardiac function improved markedly following a redo bioprosthetic mitral valve replacement. Prosthetic valve function remained satisfactory until death occurred 2 months later from refractory acute lymphocytic leukaemia. Rapid disease recurrence jeopardizing a conserved mitral valve in acute eosinophilic endomyocarditis cautions against surgical repair despite its many advantages. A bioprosthesis is associated with reduced thrombotic complications and may be the treatment of choice for this rare pathology.

Ultrastructural and immunohistochemical studies on myocardial biopsies from a patient with eosinophilic endomyocarditis

Right ventricular endomyocardial biopsy specimens from a 13-year-old boy with hypereosinophilia were studied by light and electron microscopy using the EG2 monoclonal antibody, which recognizes a common epitope of eosinophil cationic protein and eosinophil protein-X. Although the endocardial layer was of normal thickness, many eosinophils, mononuclear cells, and free eosinophil granules were observed in the endocardium and in the vicinity of degenerated myocardial cells. Under electron microscopy, many of the specific granules in and out of eosinophils had lost their crystalloid internae and displayed reversed density, and there were many degranulated eosinophils with reduced number of granules. Immunohistochemically, large amounts of eosinophil cationic protein and protein-X were observed within cardiocytes when many of them were degenerated. Deposits of the proteins were also found in some small vessels. On electron microscopy, accumulations of gold particles, which bind to eosinophil cationic protein and protein-X, were seen in association with specific granules and on the myofilaments in both degenerated and normal-appearing cardiocytes. The presence of eosinophil cationic proteins within cardiocytes may play an important role in the pathogenesis of eosinophilic endomyocardial disease.

Non-Hodgkin's lymphoma related eosinophilic endomyocardial disease

Two patients with eosinophilic endomyocardial disease related to peripheral T-cell lymphomas are reported. Both patients were free of cardiac symptoms at presentation and during follow-up. Routine two dimensional echocardiography revealed bi-apical ventricular obliteration, which was also seen on MR imaging. On the T1-weighted sequence, the thickened endocardium appeared with an isointense signal. Gadolinium DOTA provided an enhanced contrast of the internal part of the left ventricular wall. On T2-weighted sequence, a thin hypointense curvilinear structure drew a dividing line between the internal, endocardial, and the external, myocardial area. Left-ventricular systolic and diastolic functions remained unaltered during subsequent follow-up.

Synthesis of interleukin-5 by activated eosinophils in patients with eosinophilic heart diseases

Eosinophilic endomyocardial disease represents a major evolutive risk in chronic eosinophilia-associated disorders. Eosinophil granule proteins appear to be involved in cardiac injury, but the mechanisms leading to eosinophil infiltration and degranulation are not clear. Interleukin-5 (IL-5) has been recently shown to be produced by eosinophils and might play a role in both chemoattraction and degranulation of eosinophils. In four cases of eosinophilic diseases with severe cardiac failure, we evaluated the proportion of eosinophil phenotypes and the serum levels of eosinophil cationic protein (ECP) and soluble IL-2 receptor (sIL-2R), markers of disease activity in the hypereosinophilic syndromes. All four patients showed a markedly increased proportion of hypodense eosinophils with elevated serum ECP and sIL-2R levels. In all four patients, extracellular deposition of eosinophil granule proteins and features of eosinophil activation were observed in cardiac tissues. The synthesis of IL-5 by eosinophils was detected in myocardial sections and blood cells by in situ hybridization and by immunostaining with a monoclonal antibody against human IL-5. Sixty percent to 90% of tissue eosinophils expressed IL-5 mRNA and IL-5 protein. These data suggest that IL-5 can be produced by eosinophils at the sites of myocardial tissue damage and might participate in local eosinophil activation.

The eosinophil in myocardial disease

During the past decade, clinical and experimental studies have enabled the earliest forms of eosinophilic endomyocardial disease to be diagnosed by endomyocardial biopsy. Experimental studies have confirmed the suggestion that eosinophil granule constituents may be toxic to the heart, and eosinophil granule secretion products have been localized within the areas of acute necrosis. Biochemical and sequencing studies on the cationic proteins within eosinophils have confirmed their potential for causing tissue injury. In addition, the association of microvascular lesions, thrombo-embolic episodes and fibrotic lesions have all been linked to the capacity of eosinophils to produce a range of products of inflammation, including leukotriene C4, platelet activating factor and fibroblast proliferating factors. It is now suggested that these may contribute to the development of endomyocardial damage in patients with hypereosinophilia, irrespective of its cause. However, the proclivity of the endocardium for this type of lesion, and the ‘silent’ preclinical phase of the disease in many patients are important issues which remain unresolved.

DEPOSITS OF EOSINOPHIL GRANULE PROTEINS IN CARDIAC TISSUES OF PATIENTS WITH EOSINOPHILIC ENDOMYOCARDIAL DISEASE

Eosinophilic endomyocardial disease is a complication of the hypereosinophilic syndrome and of several other disorders associated with high blood eosinophil counts. Eosinophil granule proteins may be involved in the development of these lesions. This multi-centre study investigated whether these proteins could be demonstrated within the cardiac tissues of eighteen patients with eosinophilic endomyocardial disease. Serial sections of tissue taken at necropsy or at cardiac biopsy were stained for eosinophil major basic protein by indirect immunofluorescence and for eosinophil cationic protein, eosinophil protein-X, and activated eosinophils by means of alkaline-phosphatase-linked monoclonal antibodies. Activated eosinophils and secreted eosinophil granule proteins were most evident within the necrotic and later stage thrombotic lesions and were found mainly within the areas of acute tissue damage in the endocardium and in the walls of small blood vessels. These findings suggest that eosinophil granule proteins are involved in cardiac injury, producing muscle damage and vascular injury which lead to the development of endomyocardial fibrosis.

Eosinophils in eosinophilic endomyocardial disease.

Journal Article Eosinophils in eosinophilic endomyocardial disease Get access C J F Spry C J F Spry Departments of Immunology and Medicine, Royal Postgraduate Medical School and Hammersmith Hospital, London, UK Correspondence: C. Spry, D.Phil., F.R.C.P., Department of Immunology, St. George's Hospital Medical School, London SW17 0RE, UK Search for other works by this author on: Oxford Academic Google Scholar Postgraduate Medical Journal, Volume 62, Issue 728, June 1986, Pages 609–613, https://doi.org/10.1136/pgmj.62.728.609 Published: 01 June 1986

The pathogenesis of eosinophilic endomyocardial disease in patients with carcinomas of the lung

Studies were done on a patient with a carcinoma of the lung induced by hypereosinophilia who was thought to be at risk from developing eosinophilic endomyocardial disease to see whether the development of heart disease could be related to abnormalities in the morphology or kinetics of blood eosinophils. The patient was a 61-year-old man who had a partial resection of a squamous cell bronchial carcinoma of anaplastic large cell type which has spread locally. Seven months later, he developed a blood eosinophil count of 33.9 x 10(9)/1. There were only transient responses to treatment with steroids and tumor irradiation, and he died 15 weeks later. Up to 3 x 10(9)/1 blood eosinophils were degranulated, correlating with serum levels of eosinophil cationic protein. The blood half-life of 111indium-labeled eosinophils was prolonged to 53 h, but their distribution was normal. Although an unsuccessful search was made during life for the development of endomyocardial damage, at postmortem the left ventricle had features of eosinophilic endomyocardial disease in the acute necrotic stage. Among 13 other reported patients with carcinoma of the lung and hypereosinophilia, three also had endomyocardial disease or myocardial lesions. These findings confirm the suggestion that the presence in the blood of greater than 1 x 10(9)/1 degranulated eosinophils can be used to predict the development of eosinophilic endomyocardial disease before it becomes apparent clinically, and they also add weight to the hypothesis that blood eosinophil degranulation causes this complication of hypereosinophilic states.

Eosinophilic disorders affecting the myocardium and endocardium: a review.

A wide range of disorders give rise to eosinophil counts greater than 1.5 X 10(9)/l (hypereosinophilia) and cardiac injury. The best known of these is eosinophilic endomyocardial disease (Löffler's endomyocardial fibrosis), which occurs as a major complication of the idiopathic hypereosinophilic syndrome. Here the heart damage appears to be a direct result of tissue injury produced by toxic eosinophil granule proteins within the heart. However, it is not known what causes the eosinophilia in these patients, why the eosinophils degranulate, or why the endocardium is especially susceptible to this type of injury. A number of parasitic infections may give rise to eosinophilic myocarditis. This is usually the result of the presence of the parasites within the myocardium where they die within inflammatory lesions, which may be extensive. Occasionally, drug reactions and rejection of a transplanted heart may produce eosinophilic myocarditis. Allergic granulomatosis and vasculitis (the Churg-Strauss syndrome), which gives rise to granulomas involving the myocardium, and eosinophilic (hypersensitivity) myocarditis usually respond rapidly to treatment with steroids. However, diffuse myocardial involvement may lead to heart failure, and some of these patients may later develop dilated cardiomyopathy. It is concluded that the heart may be affected by a variety of diseases in which eosinophils are a prominent component in the inflammatory cell infiltrates. Eosinophils themselves may contribute to some of the myocardial cell injury which occurs in these diseases, and attempts to limit this with steroids may be worthwhile in some patients.