Löffler endocarditis: a rare cause of acute cardiac failure
© Niemeijer et al.; licensee BioMed Central Ltd. 2012
Received: 2 April 2012
Accepted: 25 September 2012
Published: 10 October 2012
We describe a patient with acute cardiogenic shock due to cardiac involvement in idiopathic hypereosinophilic syndrome (Löffler endocarditis). At the echocardiography, there was a huge mass in the left ventricular cavity, resulting in inflow- and outflow tract obstruction. The posterior leaflet of the mitral valve apparatus was completely embedded in a big (organized) thrombus mass. The patient was treated with high dose corticosteroids, however without effect. Partial remission was achieved after treatment with hydroxycarbamide. He was also treated with anticoagulants and high dose beta-blockers. The patient’s condition improved remarkably after correction of the mitral valve insufficiency by a mitral valve bioprosthesis.
KeywordsHypereosinophilic syndrome Cardiac thrombus Cardiac failure Löffler endocarditis
The hypereosinophilic syndromes (HES) are a heterogenous group of disorders marked by the sustained overproduction of eosinophils. It is a rare condition with an unknown prevalence. Diagnosis is based on three criteria: (1) an eosinophil count of more than 1500 cells per microliter for at least 6 months, (2) no other evident cause for eosinophilia, including allergic diseases and parasitic infection and (3) sign or symptoms of organ involvement by eosinophilic infiltration . Cardiac involvement is common in HES and eosinophilic myocarditis is a major cause of morbidity and mortality among patients with HES. Mitral valve involvement may lead to acute cardiac failure. We present a patient with idiopathic hypereosinophilic syndrome and severe cardiac involvement, so-called Löffler endocarditis.
A 37-year-old male patient presented to the emergency department with one month of fatigue and five days of progressive dyspnoea and fever. Three months earlier he had been diagnosed with idiopathic hypereosinophilia. Extensive diagnostic evaluation at that time revealed neither a cause for secondary eosinophilia nor any cardiac abnormalities. Oral prednisone was given for two months, but was gradually tapered since there was no decline in eosinophil count.
Acquired eosinophilia can be classified into secondary (cytokine-driven reactive phenomenon), clonal (presence of a bone marrow histological, cytogenetic or molecular marker of a myeloid malignancy) and idiopathic (neither secondary nor clonal) categories . In 1975 Chusid et al. described diagnostic criteria for idiopathic HES that remain in use today. These are blood eosinophilia of >1500 cells per microliter for more than six consecutive months, absence of an underlying cause of hypereosinophilia despite extensive diagnostic evaluation, and organ damage or dysfunction as a result of local release of the toxic contents of eosinophils . HES affects mostly men between 20 and 50 years of age, with a peak in the 4th decade of life [3, 4]. There are no published data regarding its incidence/prevalence, although the syndrome is considered rare in adults and very rare in children.
Clinical manifestations of HES are markedly heterogeneous as the disease can either be completely asymptomatic or involve multiple organs. In essence, any organ is vulnerable to eosinophilia-associated tissue damage. Thromboembolic disease involving the cardiac chambers and/or both the venous and arterial vessels is not infrequent . Cardiac involvement occurs in more than 75% of patients with HES and is the major cause of morbidity and mortality . Cardiac involvement in HES usually follows three stages. The first is an acute necrotic stage. This stage is usually neither recognized clinically nor diagnosed, like in our case. In this stage there is damage to the endocardium and infiltration of the myocardium with eosinophils and lymphocytes with histopathological evidence of myocardial necrosis and eosinophil degranulation and eosinophil micro abscesses [3, 7]. The second stage concerns thrombosis with formation of thrombi along the damaged endocardium of either one or both ventricles and occasionally in the atrium. Outflow tracts near the aortic and pulmonic valves are usually spared, although rarely thrombus may involve these valves and thrombus may form on atrioventricular valve leaflets [3, 8–10]. This stage is found in those with a mean 10-month duration of eosinophilia . In the third late fibrotic stage progressive scarring may lead to entrapment of chordae tendineae resulting in mitral and/or tricuspid valve regurgitation and endomyocardial fibrosis producing a restrictive cardiomyopathy .
To diagnose HES and Löffler endocarditis, echocardiography enables sufficient detection of thickened endocardium and intraventricular thrombus. Nevertheless, acute necrotic stage can come along with absolute normal echocardiographic findings . Endomyocardial thickening is seen in 68% of patients on echocardiography and is progressive . Apical thrombus in the presence of normal apical contraction is one of the main clues in suspected Löffler’s endomyocarditis . There are three primary goals for the management of HES: 1) reduction of peripheral and tissue levels of eosinophils; 2) prevention of end-organ damage; and 3) prevention of thrombo-embolic events in patients at risk [13, 14]. Patients without progressive organ system dysfunction typically do not require specific treatment, however, these patients should be monitored closely . Corticosteroids were initially the mainstay of HES treatment and are currently recommended as first-line therapy [15, 16]. Cytotoxic agents like hydroxyurea are indicated in HES subsets with corticosteroid resistance or when corticosteroid tapering is necessary . Interferon-alpha is an immunomodulator that reduces Th2-mediated IL-5 production, synthesis of GM-CSF and release of eosinophil-specific neurotoxin and eosinophil cationic protein and indirectly inhibits eosinophil differentiation [5, 13, 17]. It is recommended for use in HES patients with organ damage and corticosteroid/cytotoxic treatment failure [17, 18]. Allogenic stem cell transplantation has also been reported to be a potentially curative therapy. It is the ultimate therapeutic measure in case of therapeutic refractoriness or intolerance to available therapies or in patients who present with progressive life-threatening end-organ damage. The optimal preparative regime is not well established and it is associated with major morbidity and even mortality [19, 20]. Several therapies are currently under investigation as potential HES therapies, like Mepolizumab, a fully humanized monoclonal IgG anti-IL5 antibody. The secondary treatment should be directed at cardiac complications, e.g., heart failure and the presence of intracardial thrombus. In the view of subclinical progression of the cardiac involvement, especially in the primary stage of HES, our case suggests very early and aggressive anticoagulation, regardless of the initial (negative) cardiac evaluation. Occasionally, surgical therapies are needed for cardiovascular complications. Surgical experience of patients with valvular dysfunction secondary to HES is limited . Valve replacement is most often performed but the choice between a mechanical or biological prosthesis in this setting poses a difficult problem. Mechanical valves have a high incidence of recurrent obstructive thrombosis and therefor a bioprosthesis is recommended despite associated restrictive cardiomyopathy .
Hypereosinophilic syndrome is a rare cause of cardiac failure resulting in cardiogenic shock due to endomyocardial thickening and thrombus formation. Both may impede left ventricular in- and outflow tract. The risk increases when the duration of hypereosinophilia is more than ten months. Besides first line therapy (corticosteroids), early aggressive anticoagulation therapy is warranted. In more severe cases acute surgical intervention is necessary.
Written informed consent was obtained from the patient for publication of this report and any accompying images.
All the authors participated in the treatment of this patient. ND Niemeijer drafted the manuscript. PLA van Daele and NJM van der Meer helped to draft the manuscript and also revised it critically. OJL Loosveld, K Caliskan and F Oei have been involved in revising it critically. Kadir Caliskan did made the echocardiography and provided the figures. F Oei did the mitral valve replacement operation. All authors read and approved the final manuscript.
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