Eosinophilic Myocarditis Research Articles

Idiopathic Eosinophilic Myocarditis Presenting with Features of an Acute Coronary Syndrome

SummaryA 62-year-old female was admitted with severe left-sided chest pain, nausea and pre-syncope. She had widespread T wave inversion on ECG and elevated troponins and was suspected to have an acute coronary syndrome event. Invasive coronary angiogram revealed normal coronary anatomy with no flow-limiting lesions. Echocardiography and cardiac MRI revealed impaired left ventricular (LV) systolic impairment, a mobile LV apical thrombus and a moderate global pericardial effusion with no significant compromise. Full blood count analysis indicated the patient to have significant eosinophilia, and the patient was diagnosed with idiopathic eosinophilic myocarditis. She was commenced on Prednisolone and Apixaban, and eosinophil levels returned to normal after 10 days of steroids. Over the course of 3 months, the patient had a complete recovery of her LV function and resolution of the LV thrombus. This case highlights a rare, reversible case of idiopathic eosinophilic myocarditis which may present similar to acute coronary syndrome.

経時的な病状の悪化をきたした急性好酸球性心筋炎に対して，ステロイドパルス療法が奏功し，心タンポナーデによる血行動態の破綻を回避し得た1例

経時的な病状の悪化をきたした急性好酸球性心筋炎に対して，ステロイドパルス療法が奏功し，心タンポナーデによる血行動態の破綻を回避し得た1例

A case of hypereosinophilic syndrome with eosinophilic myocarditis secondary to nabumetone

Introduction: Hypereosinophilic syndromes are a group of disorders defined by an absolute eosinophil count greater than 1.5 × 109/L that leads to eosinophil-mediated end-organ damage. Cardiac involvement can range from asymptomatic inflammation of the myocardium to endomyocardial fibrosis and irreversible constrictive cardiomyopathy. Case Report: We present the case of a patient who presented with confusion and was found to have an absolute eosinophil count of 8.08 × 109/L as well as clinical findings consistent with eosinophilic myocarditis. It was determined that her clinical presentation was due to a new medication she had taken, nabumetone. Other causes of hypereosinophilia were ruled out. She improved with two days of pulse dose methylprednisolone and subsequent prednisone taper with complete resolution of her cardiomyopathy and normalization of her absolute eosinophil count. Conclusion: While there are no guidelines available for the treatment of eosinophilic myocarditis, corticosteroids should be considered in patients with evidence of cardiomyopathy in the setting of hypereosinophilia. Hypereosinophilic syndrome is an uncommonly recognized adverse event of non-steroidal anti-inflammatory drug (NSAID) therapy.

P703 A breathtaking heart. The loeffler"s endocarditis

Abstract This is a 72 year-old man known for idiopathic HES with endomyocardial fibrosis and moderate aortic regurgitation, treated with corticosteroids and antithrombotics. Two months prior to admission, he develops progressive exertional dyspnea reaching NYHA 3 class, with concomitant peripheral edema and rise in NT-proBNP. Cardiac transthoracic work-up shows a preserved left ventricular ejection fraction, but more marked dilatation with decrease in left ventricular volume due to a large echodense mass in the apex. The transmitral flow is restrictive, and the aortic regurgitation moderate. In view of this rapid evolution, resection of the left ventricular mass with concomitant aortic valve replacement is performed. Pathology confirmed eosinophilic infiltration. First described in 1975, hypereosinophilic syndrome (HES) is a rare pathology that is defined as an absolute eosinophil count (>1,5 G/L) in the peripheral blood with eosinophil-mediated organ damage and /or dysfunction. We know three mains categories; primary (or neoplastic), secondary (or reactive) and idiopathic. Cardiac involvement is uncertain and cardiac injury does not clearly correlate with degree of peripheral eosinophilia. Heart tissue damage evolves through three stages (necrotic, intermediate and fibrotic). Endomyocardial fibrosis and eosinophilic myocarditis, also known as "Loeffler’s endocarditis", are major causes of morbidity and mortality among patients with HES. Echocardiography plays a crucial role in initial diagnosis of endomyocardial fibrosis, displaying myocardial wall thickening, signs of restriction (mitral inflow with large E wave and small A wave; E/A ratio greater than 2, short deceleration time less than 150 ms) and intracardiac thrombus (fixed mass embedding left ventricular apex). Valve regurgitation is another possible complication due to entrapment of the chordae tendinae and/or leaflets during the fibrotic stage of this disease. Cardiac MRI is another important diagnostic tool for precising cardiac involvement. Despite of steadily improving noninvasive diagnostic imaging methods, endomyocardial biosy still remains the gold standard exam and ultrasounds work-up is crucial for follow-up. In conclusion, endomyocardial fibrosis is a rare cause of restrictive cardiomyopathy characterized by echocardiographic sign of elevated filling pressure, progressive endomyocardial thickening, valve regurgitation and possible intracardiac thrombus formation. This case underlines the importance of echocardiography in initial diagnosis and regular follow-up of this type of patients, in order to adapt medical treatment and monitor hemodynamic evolution of the restrictive physiology and of valvular damage. Abstract P703 Figure. HES-3

Atypical parasitic lesions in slaughtered cattle in Southern Brazil.

In this study, we described the morphological features and unusual presentations of hydatidosis, fasciolosis, and eosinophilic myositis caused by Sarcocystis species diagnosed at the slaughterhouse lines. Twenty-seven samples of atypical parasitic lesions from distinct cattle were evaluated, of which 12 corresponded to hydatidosis, 11 to fasciolosis, and 4 to eosinophilic sarcocystosis. Hydatid cysts were observed mainly in the heart, with all cases involving the left ventricle. Fasciolosis lesions involved mainly the lungs, and were characterized by a focal nodular elevated area involving the edges of the lobes. Intralesional trematodes were observed in three cases. Sarcocystosis lesions were observed in four cases, and lesions were primarily located in the skeletal and cardiac muscles. Grossly, they presented as focal or focally extensive streaks, patches, or numerous nodules that were greenish to mildly yellowish. Histologically, all the cases had intralesional ruptured cysts of Sarcocystis that were associated with severe eosinophilic myositis and myocarditis. Parasitic lesions in atypical locations and/or with aberrant responses should be promptly identified because it may mistakenly diagnosed as other potentially zoonotic diseases, such as cysticercosis and tuberculosis.

Clinicopathological manifestations of myocarditis in a heart failure population.

Myocarditis continues to present challenges in diagnosis and management. The goal of this study is to determine the occurrence and manifestations of myocarditis in a heart failure (HF) population. The analyzed patients had acute or persistent HF and were referred over a 6-year period to a quaternary HF center for advanced HF therapies including mechanical circulatory support, left ventricular assist device (LVAD) implantation, and/or heart transplantation. The histopathological diagnosis of myocarditis was made based on the presence of an inflammatory infiltrate of the myocardium, typically with associated cardiomyocyte (CMC) damage, combined as indicated with immunohistochemical and molecular biology characterization. The pathological findings were correlated with a panel of clinical parameters and clinical course of the patients. Myocarditis was identified in 36 patients, with initial diagnoses made in 10 (40%) of 25 by endomyocardial biopsy (EMB), 1 by atrial biopsy (maze procedure), 7 (2.1%) of 331at LVAD implantation, and 18 (7.8%) of 229 in the explanted heart. There were 20 cases of lymphocytic myocarditis, 4 cases of giant cell myocarditis, 3 cases of eosinophilic myocarditis, and 9 cases of lymphohistocytic with granulomas myocarditis - cardiac sarcoidosis. EMB was performed in 25 patients and was positive in 10 (40%) of cases. Myocarditis was found in 23 explanted hearts including 18 cases de novo and 5 cases with a previously positive specimen. Of the 23 explanted hearts, 21 were nonischemic cardiomyopathy and 2 were ischemic cardiomyopathy. Our findings show that, in patients presenting to a quaternary medical center, myocarditis can be manifest as acute HF as well as a complicating factor in chronic HF.

Eosinophilic Myo-Pericarditis Presenting as Cardiac Tamponade

Eosinophilic myocarditis is a rare and acute life threatening condition often associated with drug reactions, eosinophilic granulomatous polyangiitis (formerly Churg-Strauss syndrome), Loeffler endomyocardial disease, parasite infections, and idiopathic hypereosinophilic syndrome. We describe a case of eosinophilic granulomatous polyangiitis presenting as progressive pericardial effusion and cardiac tamponade.

M407 MEPOLIZUMAB FOR TREATMENT-REFRACTORY EOSINOPHILIC MYOCARDITIS IN AN INFANT

Eosinophilic myocarditis is a rare form of myocarditis caused by a range of diseases. Though the underlying etiology can guide therapy, the mainstay of treatment is systemic corticosteroids, with limited options for refractory disease.

Severe Eosinophilic Myocarditis in the Portion of Left Ventricular Wall Excised to Insert a Left Ventricular Assist Device for Severe Heart Failure

Described herein are 3 adults in whom histologic study of the left ventricular myocardium excised ("LV core") to insert a left ventricular assist device (LVAD) disclosed severe acute myocarditis and the inflammatory cells included numerous eosinophils (eosinophilic myocarditis). Examination of the clinical records disclosed elevated absolute eosinophil counts at the time of insertion of the LVAD and the counts rapidly (<30 days) returned to normal after the operation. Because of the numerous medications that each patient was taking at the time of LVAD insertion, identification of a specific initiating medication as its cause was not possible. Of the 3 patients, 2 had idiopathic-dilated cardiomyopathy and 1 had ischemic cardiomyopathy and each had had heart failure for years. The eosinophilic myocarditis in these 3 patients appears to have been transient and superimposed on the earlier cardiomyopathy.

Heart disease in a mutant mouse model of spontaneous eosinophilic myocarditis maps to three loci

BackgroundHeart disease (HD) is the major cause of morbidity and mortality in patients with hypereosinophilic diseases. Due to a lack of adequate animal models, our understanding of the pathophysiology of eosinophil-mediated diseases with heart complications is limited. We have discovered a mouse mutant, now maintained on an A/J inbred background, that spontaneously develops hypereosinophilia in multiple organs. Cellular infiltration into the heart causes an eosinophilic myocarditis, with affected mice of the mutant line (i.e., A/JHD) demonstrating extensive myocardial damage and remodeling that leads to HD and premature death, usually by 15-weeks old.ResultsMaintaining the A/JHD line for many generations established that the HD trait was heritable and implied the mode of inheritance was not too complex. Backcross and intercross populations generated from mating A/JHD males with females from four different inbred strains produced recombinant populations with highly variable rates of affected offspring, ranging from none in C57BL/6 J intercrosses, to a few mice with HD using 129S1/SvImJ intercrosses and C57BL/6 J backcrosses, but nearly 8% of intercrosses and > 17% of backcrosses from SJL/J related populations developed HD. Linkage analyses of these SJL/J derived recombinants identified three highly significant loci: a recessive locus mapping to distal chromosome 5 (LOD = 4.88; named Emhd1 for eosinophilic myocarditis to heart disease-1); and two dominant variants mapping to chromosome 17, one (Emhd2; LOD = 7.51) proximal to the major histocompatibility complex, and a second (Emhd3; LOD = 6.89) that includes the major histocompatibility region. Haplotype analysis identified the specific crossovers that defined the Emhd1 (2.65 Mb), Emhd2 (8.46 Mb) and Emhd3 (14.59 Mb) intervals.ConclusionsThese results indicate the HD trait in this mutant mouse model of eosinophilic myocarditis is oligogenic with variable penetrance, due to multiple segregating variants and possibly additional genetic or nongenetic factors. The A/JHD mouse model represents a unique and valuable resource to understand the interplay of causal factors that underlie the pathology of this newly discovered eosinophil-associated disease with cardiac complications.

P5558Conditions associated with eosinophilic myocarditis: a national population-based cross sectional study

Abstract Background Eosinophilic Myocarditis (EM) is a rare but potentially fatal form of myocardial inflammation, characterized by eosinophilic infiltration of the myocardium. Due to its rare occurrence, there has been no descriptive study of EM on the population level. Purpose Our study aims to use a large national database to describe the prevalence, associated clinical conditions and hospital outcomes of EM. Methods We analyzed the 2016 National Inpatient Sample Database (NIS) for all hospitalizations with a diagnosis of EM. Prevalence and baseline characteristics of EM were described and compared with non-EM admissions, as well as associated clinical conditions. Results In 2016, there were 170 admissions with a diagnosis of EM. Among those, White represented the major ethnic group, followed by African American, Asian/Pacific Islander/Native American, and Hispanic (Fig. 1). There was no significant gender predisposition to EM, but EM patients presented at an older age compared with the general population. The prevalence of Systemic Lupus Erythematosus, Myeloproliferative disorders, Acute Coronary Syndrome, Heart Failure, Arrhythmia, Heart Transplant, Eosinophilic Granulomatosis with Polyangiitis, Eosinophilia was significantly higher in EM patients. Also, EM patients had higher mortality. (Table 1) Table 1. A comparison of EM and Non-EM EM (n=170) Non-EM (n=35,675,421) P-value Demographic Age, years 61.53±2.93 49.00±0.19 P=0.007 Female, % 50.00±7.80 56.72±0.10 P=0.38 Clinical Conditions Systemic Lupus Erythematosus, % 2.94±2.74 0.50±0.01 P=0.03 Myeloproliferative Disorder, % 8.82±4.33 0.52±0.01 P&lt;0.001 Acute Coronary Syndrome, % 20.59±6.07 6.55±0.06 P&lt;0.001 Heart Failure, % 61.76±9.42 13.29±0.10 P&lt;0.001 Arrhythmia, % 14.71±7.25 2.44±0.03 P&lt;0.001 Heart Transplant, % 2.94±2.84 0.06±0.005 P&lt;0.001 EGPA, % 2.94±2.92 0.00±0.00 P&lt;0.001 Eosinophilia, % 5.88±3.95 0.07±0.002 P&lt;0.001 Outcome Mortality, % 8.82±4.83 1.91±0.02 P=0.003 Data is presented in the format of the mean ± standard error. Figure 1. Racial distribution of EM patients Conclusion(s) Eosinophilic Myocarditis is rare, and it's associated with autoimmune diseases, cardiac complications, and worse hospital outcomes.

2421Immunosuppressive therapy and prognosis in biopsy-proven fulminant lymphocytic myocarditis requiring veno-arterial extracorporeal membranous oxygenation support

Abstract Background Fulminant myocarditis is one of the fatal diseases for which effective management has not yet been established. Immunosuppressive therapy (IST) using corticosteroid has been actively applied to giant cell or eosinophilic myocarditis, there is no consensus on the efficacy of lymphocytic myocarditis, which is suspected of involving viral infection. Actually, IST for lymphocytic myocarditis is not recommended in the European Society of Cardiology guidelines, but in the Japanese Circulation Society guidelines, it is approved for use in refractory cases in the absence of curative therapy for myocarditis established. Purpose The purpose of this study was to explore the potential efficacy of immunosuppressive therapy on acute phase in fulminant lymphocytic myocarditis (FLM) requiring veno-arterial extracorporeal membranous oxygenation (VA-ECMO) support. Method We conducted CHANGE-PUMP study that was retrospectively enrolled 99 patients with fulminant myocarditis required VA-ECMO support in the Tokai area (central part of Japan) for the past 20 years. Lymphocytic myocarditis was defined by pathological category. Patients were divided into two groups depending on whether IST using corticosteroid was performed in the clinical course. Results: Sixty-six patients were pathologically diagnosed as fulminant myocarditis by endomyocardial biopsy, of which only 49 patients were FLM. IST were indicated in 8 (16%) out of 49 patients of FLM (IST group; n=8, non-IST group; n=41). Kaplan-Meier survival analysis showed a lower survival rate in the IST group than in the non-IST group (p=0.073). However, in all cases, based on our guidelines, IST was initiated after becoming refractory to MCS treatment. Immunosupressive therapy and prognosis Conclusion In the retrospective analysis, biopsy-proven FLM patients with IST required VA-ECMO support had low survival rates. However, the timing of IST introduction was late and concerned. In the present era when advanced mechanical support appears and the survival rate of fulminant myocarditis is expected to improve, a multicenter prospective study is needed to establish an indication of IST in the acute phase of fulminant myocarditis.

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS WITH CARDIAC INVOLVEMENT

SESSION TITLE: Case Report Semifinalists 12 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA), a vasculitis of small- and medium-sized vessels, can be difficult to diagnose due to its diversity of manifestations. We present the case of a patient with respiratory failure and a prolonged course of symptoms prior to being diagnosed with EGPA and successfully treated. CASE PRESENTATION: A 51-year-old male with a history of asthma presented to the ED with cough, hemoptysis, fevers, and weight loss. Chest imaging demonstrated tree-in-bud opacities and mediastinal lymphadenopathy, found to be reactive lymph nodes on biopsy. Bronchoalveolar lavage showed eosinophilia and CBC revealed peripheral eosinophilia. Prednisone was started for presumed chronic eosinophilic pneumonia. He was later admitted to the MICU for worsening dyspnea and hemoptysis, was intubated for respiratory distress and noted to have multilobar infiltrates. Echocardiogram revealed a reduced ejection fraction (EF) of 21-25%, and angiogram ruled out ischemic cardiomyopathy. Despite steroids, his eosinophilia persisted and he was found to have a positive p-ANCA titer of 1:160. Purpuric lesions were noted on his lower extremities and skin biopsy demonstrated eosinophilic and lymphocytic infiltration. Given the suspicion for EGPA, cardiac MRI was performed and revealed a dilated left ventricle, severe global dysfunction, and delayed enhancement, consistent with eosinophilic myocarditis. The patient was transferred for endomyocardial biopsy, which revealed an eosinophil-rich interstitial infiltrate with associated myocardial necrosis, confirming his diagnosis of EGPA with cardiac involvement. He was treated with steroids and cyclophosphamide, with improvement in his pulmonary lesions on CT chest, increase in his EF to 36% on repeat cardiac MRI, and resolution of his peripheral eosinophilia. DISCUSSION: Our case illustrates a wide variety of manifestations of EGPA and the importance of keeping it in the differential diagnosis when such symptoms present. With treatment, 5-year overall survival of EGPA is greater than ninety percent. Exact triggers for EGPA are unknown, though it almost always presents in asthmatics with high allergen burden, both of which were features of our patient. Our patient had elevated ANCA titers; interestingly, it has been shown that ANCA positive patients are more likely to present with cardiac involvement(1). Furthermore, it has been demonstrated that extensive organ system involvement, especially cardiac, in EGPA is a poor prognostic factor(2); this necessitated the prompt diagnosis and initiation of treatment for our patient. CONCLUSIONS: This case highlights the importance of maintaining a high index of suspicion for EGPA in an asthmatic patient with new pulmonary, cardiac, skin, and neurologic symptoms; though EGPA is a rare disease, its prompt treatment can be of the utmost importance. Reference #1: Greco, A., Rizzo, MI., De Virgilio, A., et al. Churg-Strauss syndrome. Autoimmunity Reviews. (2015) 14(4): 341-348. Reference #2: Guillevin L., Pagnoux C., Seror, R. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculititdes based on the French Vasculitis Study Group (FSVG) cohort. Medicine (Baltimore). (2011) 90(1): 19-27. DISCLOSURES: No relevant relationships by Carolyn Bendor-Grynbaum, source=Web Response No relevant relationships by Amy Espinal, source=Web Response No relevant relationships by Sushilkumar Gupta, source=Web Response No relevant relationships by Yizhak Kupfer, source=Web Response No relevant relationships by Radhames Ramos De Oleo, source=Web Response No relevant relationships by Chanaka Seneviratne, source=Web Response No relevant relationships by Shyam Shankar, source=Web Response No relevant relationships by Parita Soni, source=Web Response No relevant relationships by Shyam Sundaresh, source=Web Response

2422Outcome of histologically-proven fulminant versus acute non-fulminant myocarditis with left ventricular systolic dysfunction. Evidence from the International Registry on Acute Myocarditis

Abstract Background Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular (LV) dysfunction requiring inotropes and/or mechanical circulatory support. Based on a retrospective single-center study published in 2000, patients with FM were considered to have better outcomes than those affected by acute non-fulminant myocarditis (NFM) presenting with LV systolic dysfunction (LVSD). Recently, this tenet was challenged, though substantial disagreement still exists. Purpose Aim of the present study is to provide additional evidence on the outcome of FM and to ascertain if patient stratification based on the main histologic subtypes can provide additional prognostic information. Methods Two hundred and twenty patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms &lt;30 days) presenting with LVSD were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The primary endpoint was the occurrence of cardiac death or heart transplant (HTx) within 60 days from admission and at long-term follow-up. Results Patients with FM (N=165) had significantly higher rates of cardiac death and HTx compared with those with NFM (N=55), both at 60 days (28.0% vs. 1.8%, p=0.0001) and at 7-year follow up (47.7% vs. 10.4%, p&lt;0.0001; Figure). At Cox-multivariate analysis, the histologic subtype emerged as a further variable affecting outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis both at 60 days (62.5% vs. 26.3% vs. 21.0%) and at 3 years (81.3% vs. 39.9% vs. 37.3%, overall p&lt;0.0001). In a sub-analysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with NFM both at 60 days (19.5% vs. 0%, p=0.005) and up to 7 years (41.4% vs. 3.1%, p=0.0004). Outcome of FM vs NFM Conclusions The results of this international registry confirm that patients with FM have higher rates of cardiac death and HTx both in the short and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition. Acknowledgement/Funding None

A Case Series of Biopsy-Proven Eosinophilic Myocarditis at a Tertiary Care Center

BackgroundThere is limited published literature on acute eosinophilic myocarditis (EM), a rare form of acute myocarditis, wherein eosinophils invade the myocardium with wide-ranging clinical sequalae. We aim to describe our experience in the largest contemporary case series of histologically-proven EM.MethodsTwo authors independently reviewed the surgical pathology and autopsy databases for acute EM (01/2009 to 12/2017). Only patients with endomyocardial biopsy/autopsy and clinical course consistent with acute EM were included. We abstracted demographic data, comorbidities, clinical diagnostics, and clinical outcomes.ResultsSeven patients had acute EM (Table). The average age was 53-years and five subjects were women. The most common etiology of EM was idiopathic. Five patients had peripheral eosinophilia. Three patients had elevated pulmonary capillary wedge pressure and three patients had reduced cardiac output. Six patients were treated with steroids, four of whom received IV pulse dosed steroids. Two patients required intra-aortic balloon pump support, one of whom subsequently underwent durable left ventricular assist device implantation. Two patients died during index hospitalization, one of septic shock and one of refractory ventricular tachycardia.ConclusionThe etiologies, clinical presentation, and course of acute EM varied widely. Prompt diagnosis, treatment with immunosuppression, and circulatory support may reduce cardiovascular mortality in this population. There is limited published literature on acute eosinophilic myocarditis (EM), a rare form of acute myocarditis, wherein eosinophils invade the myocardium with wide-ranging clinical sequalae. We aim to describe our experience in the largest contemporary case series of histologically-proven EM. Two authors independently reviewed the surgical pathology and autopsy databases for acute EM (01/2009 to 12/2017). Only patients with endomyocardial biopsy/autopsy and clinical course consistent with acute EM were included. We abstracted demographic data, comorbidities, clinical diagnostics, and clinical outcomes. Seven patients had acute EM (Table). The average age was 53-years and five subjects were women. The most common etiology of EM was idiopathic. Five patients had peripheral eosinophilia. Three patients had elevated pulmonary capillary wedge pressure and three patients had reduced cardiac output. Six patients were treated with steroids, four of whom received IV pulse dosed steroids. Two patients required intra-aortic balloon pump support, one of whom subsequently underwent durable left ventricular assist device implantation. Two patients died during index hospitalization, one of septic shock and one of refractory ventricular tachycardia. The etiologies, clinical presentation, and course of acute EM varied widely. Prompt diagnosis, treatment with immunosuppression, and circulatory support may reduce cardiovascular mortality in this population.

Fulminant Versus Acute Nonfulminant Myocarditis in Patients With Left Ventricular Systolic Dysfunction

BackgroundFulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. ObjectivesThis study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. MethodsA total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms <30 days) all presenting with left ventricular systolic dysfunction were included in a retrospective, international registry comprising 16 tertiary hospitals in the United States, Europe, and Japan. The main endpoint was the occurrence of cardiac death or heart transplantation within 60 days from admission and at long-term follow-up. ResultsPatients with FM (n = 165) had significantly higher rates of cardiac death and heart transplantation compared with those with NFM (n = 55), both at 60 days (28.0% vs. 1.8%, p = 0.0001) and at 7-year follow-up (47.7% vs. 10.4%, p < 0.0001). Using Cox multivariate analysis, the histologic subtype emerged as a further variable affecting the outcome in FM patients, with giant cell myocarditis having a significantly worse prognosis compared with eosinophilic and lymphocytic myocarditis. In a subanalysis including only adults with lymphocytic myocarditis, the main endpoints occurred more frequently in FM compared with in NFM both at 60 days (19.5% vs. 0%, p = 0.005) and at 7-year follow up (41.4% vs. 3.1%, p = 0.0004). ConclusionsThis international registry confirms that patients with FM have higher rates of cardiac death and heart transplantation both in the short- and long-term compared with patients with NFM. Furthermore, we provide evidence that the histologic subtype of FM carries independent prognostic value, highlighting the need for timely endomyocardial biopsy in this condition.

Characterization of a mouse model of hypereosinophilia-associated heart disease.

Hypereosinophilic syndrome is characterized by sustained and marked eosinophilia leading to tissue damage and organ dysfunction. Morbidity and mortality occur primarily due to cardiac and thromboembolic complications. Understanding the cause and mechanism of disease would aid in the development of targeted therapies with greater efficacy and fewer side effects. We discovered a spontaneous mouse mutant in our colony with a hypereosinophilic phenotype. Mice develop peripheral blood eosinophilia; infiltration of lungs, spleen, and heart by eosinophils; and extensive myocardial damage and remodeling. This ultimately leads to heart failure and premature death. Histopathological assessment of the hearts revealed a robust inflammatory infiltrate composed primarily of eosinophils and B-lymphocytes, associated with myocardial damage and replacement fibrosis, consistent with eosinophilic myocarditis. In many cases, hearts showed dilatation and thinning of the right ventricular wall, suggestive of an inflammatory dilated cardiomyopathy. Most mice showed atrial thrombi, which often filled the chamber. Protein expression analysis revealed overexpression of chemokines and cytokines involved in innate and adaptive immunity including IL-4, eotaxin, and RANTES. Disease could be transferred to wild-type mice by adoptive transfer of splenocytes from affected mice, suggesting a role for the immune system. In summary, the pathologies observed in the mutant lines are reminiscent of those seen in patients with hypereosinophilia, where cardiac-related morbidities, like congestive heart failure and thrombi, are the most common causes of death. As such, our model provides an opportunity to test mechanistic hypotheses and develop targeted therapies.NEW & NOTEWORTHY This article describes a new model of heart disease in hypereosinophilia. The model developed as a spontaneous mouse mutant in the colony and is characterized by peripheral blood eosinophilia and infiltration of lungs, spleen, and heart by eosinophils. In the heart, there is extensive myocardial damage, remodeling, fibrosis, and thrombosis, leading to heart failure and death. The immune microenvironment is one of increased innate and adaptive immunity, including Th1 and Th2 cytokines/chemokines. Finally, adoptive transfer of splenocytes transfers disease to recipient mice. In summary, this model provides an opportunity to test mechanistic hypotheses and develop targeted therapies for this rare but devastating disease.

A RARE CASE OF MINOCYCLINE INDUCED EOSINOPHILIC MYOCARDITIS

Eosinophilic myocarditis (EM) is a rare form of myocarditis characterized by myocardial inflammation with eosinophils, often in association with elevated levels of circulating blood eosinophils greater than 1,500. Often presenting with a constellation of cardiac symptoms, EM is usually associated

A RARE CAUSE AND COMPLICATION OF EOSINOPHILIA DUE TO A COMMON HEART FAILURE MEDICATION

Cardiac medications are an infrequent cause of peripheral eosinophilia. Dobutamine has been implicated in eosinophilic myocarditis, however there are no reported cases of milirinone-induced peripheral eosinophilia and eosinophilic cystitis. A 69-year-old male with persistent atrial fibrillation on

EOSINOPHILIC MYO-PERICARDITIS PRESENTING AS CARDIAC TEMPONADE

Eosinophilic myocarditis is a rare and acute life threatening condition often associated with drug reactions, eosinophilic granulomatous polyangiitis (formerly Churg-Strauss syndrome), Loeffler endomyocardial disease, parasite infections, and idiopathic hypereosinophilic syndrome. We describe a case