Eosinophilic Heart Disease Research Articles

Eosinophilic heart disease: diagnostic and prognostic assessment by cardiac magnetic resonance.

Eosinophilic heart disease (EHD) is a rare cardiac condition with a wide spectrum of phenotypes. The diagnostic and prognostic value of cardiac magnetic resonance (CMR) in EHD remains unknown. This was a retrospective analysis of 250 patients with eosinophilia referred for a CMR scan (period 2000-2020). CMR data sets and clinical/laboratory data were collected. Patients were followed up for a mean of 24 months (range 1-224) for the composite endpoint of death, acute coronary syndrome, hospitalization for acute heart failure, malignant ventricular arrhythmias, or the need for implantable cardiac defibrillator/pacemaker. The main objectives were to explore the diagnostic value of CMR in EHD; relationships between cardiac function, late gadolinium enhancement (LGE), and EHD phenotypes; and the prognostic value of fibrosis and oedema by CMR. The prevalence of findings compatible with EHD was 39% (patients with cardiac symptoms: 57% vs. screening: 20%, P < 0.001). EHD phenotypes included subendocardial LGE (n = 58), mid-wall/subepicardial LGE (n = 26), pericarditis (n = 5) or dilated cardiomyopathy (n = 8). Myocardial oedema was present in 10% of patients. Intracardiac thrombi (7%) were associated with EHD phenotype (χ2=47.3, P = 1.3×10-8). LGE extent correlated with LVEDVi (rho = 0.268, P = 5.3×10-5) and LVEF (rho=-0.415, P = 8.6×10-11). A CMR scan positive for EHD [hazard ratio (HR) = 5.61, 95% confidence interval (CI): 1.82-17.89, P = 0.0026] or a subendocardial LGE pattern (HR = 5.13, 95% CI: 1.29-20.38, P = 0.020) were independently associated with the composite clinical endpoint. The diagnostic yield of CMR screening in patients with persistent eosinophilia, even if asymptomatic, is high. The extent of subendocardial fibrosis correlates with LV remodelling and independently predicts clinical outcomes in patients with eosinophilia.

Eosinophilic Heart Disease: A Case Report and Review of Literature

Eosinophilic Heart Disease: A Case Report and Review of Literature

Abstract 17547: Syncope and Inferior ST Elevations: A Diagnosis Within the Heart

A 53 year old woman with a history of diabetes and hypertension presented with syncope, hypotension, and electrocardiography demonstrating inferior ST elevations. The week prior to admission she treated an episode of left knee pain with an admixture of Chinese herbs. Two days prior to presentation she noted the onset of fevers, myalgias and dizziness culminating in syncope the day of admission. Initial electrocardiogram demonstrated complete heart block and junctional escape with inferior ST elevations. Cardiac catheterization demonstrated no epicardial coronary disease. Laboratory studies revealed acute kidney injury, elevated cardiac biomarkers, and a normal white blood cell count with normal differential. Upon transfer to our hospital, the patient was hypotensive requiring temporary ventricular pacing and vasopressor support. Echocardiogram demonstrated severe systolic dysfunction with LVEF of 31%. On arrival, she was noted to have episodes of monomorphic ventricular tachycardia. Etiologies of fulminant myocarditis considered included viral (lymphocytic), giant cell myocarditis, and sarcoid a well as acute eosinophilic myocarditis given recent ingestion of novel herbal mixture. Given the potential for steroid-responsive etiologies, endomyocardial biopsy was performed with institution of mechanical support ( intra-aortic balloon pump) and administration of parenteral steroids. Inotropic and mechanical support were weaned within 72 hours of administration of steroids and she demonstrated normalization of electrical conduction. Biopsy demonstrated acute necrotizing eosinophilic myocarditis (ANEM). Cardiac MRI demonstrated acute myocarditis, subacute inferior infarct, and no LV thrombus. ANEM represents an often fatal, fulminant form of eosinophilic heart disease and can present without systemic eosinophilia. Triggers can include antecedent viral illness and drug hypersensitivity (including herbal mixtures). Eosinophilic proteins can stimulate platelet aggregation and coronary vasoconstriction. Considered mechanisms of inferior infarct included LV thrombus with coronary embolism. The patient was treated with steroids and anticoagulation with recovery of baseline cardiopulmonary function.

Fatal Eosinophilic Myocarditis Develops in the Absence of IFN-γ and IL-17A

CD4(+) T cells play a central role in inflammatory heart disease, implicating a cytokine product associated with Th cell effector function as a necessary mediator of this pathophysiology. IFN-γ-deficient mice developed severe experimental autoimmune myocarditis (EAM), in which mice are immunized with cardiac myosin peptide, whereas IL-17A-deficient mice were protected from progression to dilated cardiomyopathy. We generated IFN-γ(-/-)IL-17A(-/-) mice to assess whether IL-17 signaling was responsible for the severe EAM of IFN-γ(-/-) mice. Surprisingly, IFN-γ(-/-)IL-17A(-/-) mice developed a rapidly fatal EAM. Eosinophils constituted a third of infiltrating leukocytes, qualifying this disease as eosinophilic myocarditis. We found increased cardiac production of CCL11/eotaxin, as well as Th2 deviation, among heart-infiltrating CD4(+) cells. Ablation of eosinophil development improved survival of IFN-γ(-/-)IL-17A(-/-) mice, demonstrating the necessity of eosinophils in fatal heart failure. The severe and rapidly fatal autoimmune inflammation that developed in the combined absence of IFN-γ and IL-17A constitutes a novel model of eosinophilic heart disease in humans. This is also, to our knowledge, the first demonstration that eosinophils have the capacity to act as necessary mediators of morbidity in an autoimmune process.

The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia

Imatinib is the treatment of choice for FIP1L1/PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P CEL), but its optimal dosing, duration, and possibility of discontinuation are still a matter of debate. A retrospective multicenter study was conducted with 44 F/P CEL patients identified in the French Eosinophil Network and treated with imatinib. The most frequently involved systems were skin (57%), spleen (52%), and lung (45%), and eosinophilic heart disease was observed in 15 patients (34%). Complete hematologic response (CHR) was obtained in all patients, and complete molecular response (CMR) in 95% of patients (average initial imatinib dose, 165 mg/d). For 29 patients the imatinib dose was tapered with a maintenance dose of 58 mg/d (±34 mg/d), allowing sustained CHR and CMR. None of the patients developed resistance during a median follow-up of 52.3 months (range, 1.4-97.4 mo). Imatinib was stopped in 11 patients; 6 of the patients subsequently relapsed, but 5 remained in persistent CHR or CMR (range, 9-88 mo). These results confirm that an initial low-dose regimen of imatinib (100 mg/d) followed by a lower maintenance dose can be efficient for obtaining long-term CHR and CMR. Our data also suggest that imatinib can be stopped in some patients without molecular relapse.

Eosinophilic heart disease in a paediatric patient

A 12-year-old child with no previous medical history was referred with a 4-day history of cough, shortness of breath, and peripheral blood eosinophilia. Transthoracic echocardiography showed a soft tissue infiltrating the left ventricular free wall, the lateral mitral annulus, and the mitral valve leaflets. A soft tissue strand connecting the lateral left atrial wall and mitral leaflets across the mitral valve orifice was also identified, causing reduced opening and functional mitral stenosis. The diagnosis of Löeffler endocarditis was made, and after 10 weeks of treatment with oral prednisolone, there was complete resolution of symptoms and of the infiltrative tissue with normalization of mitral valve function. The present case highlights some atypical features of eosinophilic heart disease-like occurrence in paediatric age, the complete preservation of the right ventricle and left ventricular apex, and the presentation with mitral stenosis compared with mitral regurgitation typically observed in the late phase of the disease.

Restrictive cardiomyopathies

Restrictive cardiomyopathies constitute a heterogenous group of heart muscle conditions that all have, in common, the symptoms of heart failure. Diastolic dysfunction with preserved systolic function is often the only echocardiographic abnormality that may be noted, although systolic dysfunction may also be an integral part of some specific pathologies, particularly in the most advanced cases such as amyloid infiltration of the heart. By far, the majority of restrictive cardiomyopathies are secondary to a systemic disorder such as amyloidosis, sarcoidosis, scleroderma, haemochromatosis, eosinophilic heart disease, or as a result of radiation treatment. The much more rare diagnosis of idiopathic restrictive cardiomyopathy is supported only by the absence of specific pathology on either endomyocardial biopsies or at post-mortem. Restrictive cardiomyopathy is diagnosed based on medical history, physical examination, and tests: such as blood tests, electrocardiogram, chest X-ray, echocardiography, and magnetic resonance imaging. With its wide availability, echocardiography is probably the most important investigation to identify the left ventricular dysfunction and should be performed early and by groups that are familiar with the wide variety of aetiologies. Finally, on rare occasions, the differential diagnosis from constrictive pericarditis may be necessary.

Huge coronary embolism in a patient with eosinophilic heart disease

Huge coronary embolism in a patient with eosinophilic heart disease

Eosinophilic Heart Disease in Acute Myeloproliferative Disorder

A 34-year-old man with no past medical history presented to our emergency department with facial droop and dysarthria. He had a 1-day history of dyspnea and nonproductive cough, which he attributed to a viral illness. Examination was notable only for the neurological abnormalities in the chief complaint, which resolved during the emergency department evaluation. A 12-lead ECG showed sinus tachycardia, a prolonged corrected QT interval (530 ms), and T-wave inversion suggestive of ischemia (Figure 1). MRI of the brain was negative for acute stroke. Laboratory values were notable for a hemoglobin of 8.8 g/dL, white blood cell count of 75 400 cells/mL with absolute eosinophilia to 22 620 cells/mL, and a platelet count of 31 000/mL. Troponin T was elevated to 0.40 μg/mL (normal <0.03) with a normal creatine kinase of 22 U/L. An urgent transthoracic echocardiogram demonstrated a …

Early Differential Resolution of Right and Left Ventricular Obliteration in Löffler Endocarditis After Chemotherapy and Anticoagulation

A 27-year-old woman diagnosed of T-cell non-Hodgkin lymphoma was referred to our hospital for allogenic hemopoietic stem cell transplantation. In childhood, the patient was diagnosed with hypereosinophilic syndrome. One week before admission, the patient started to develop progressive dyspnea. On chest x-ray, there were signs consistent with congestive heart failure. Her white cell count was 5990/mm3 with 59% eosinophils. A transthoracic echocardiogram disclosed a complete obliteration of the apexes of both ventricles, which were filled with a mildly echogenic material consistent with fibrosis or thrombosis. The right and left atria were enlarged, and pulsed wave Doppler examination showed a restrictive left ventricular (LV) filling pattern (Figure 1A through 1C). All of these findings were compatible with the diagnosis of Loffler endocarditis. The patient was anticoagulated and received conventional treatment for heart failure, resulting in clinical improvement. One week after admission, chemotherapy with fludarabine and melphalan was started, and a nonmyeloablative transplantation was carried out using hematopoietic progenitors from a human leukocyte antigen–compatible brother. Four weeks after chemotherapy, a repeat echocardiogram showed the total disappearance of the LV obliteration and a normal filling …

Kimura's disease in a patient with idiopathic dilated cardiomyopathy on ambulatory peritoneal dialysis

Sir, Kimura’s disease, endaemic in Asia, manifests as solitary or multiple subcutaneous nodules in the head and neck, marked peripheral eosinophilia and elevated serum IgE [1]. Many cases of this are associated with nephrotic syndrome of unknown cause; and there is no evidence in these patients for a relationship between the end-stage renal disease and Kimura’s disease. We describe a patient on chronic ambulatory peritoneal dialysis (CAPD) with a unique concomitant presentation of idiopathic dilated cardiomyopathy and Kimura’s disease. A 17-year-old Taiwanese boy was diagnosed as having nephrotic syndrome when he was 12 years old, and he was treated with oral prednisolone. Then he was lost to follow-up, having turned to traditional Chinese herbal drugs. At the age of 16, he presented at our hospital again with dyspnoea and oliguria. Haemodialysis was performed initially because of acute pulmonary oedema; then he received CAPD. Idiopathic eosinophilia was noted at this admission [white blood cells (WBCs), 6050/ml; segmented neutrophils, 59.4%; lymphocytes, 10.9%; monocytes, 4.1%; eosinophils, 25.3%; basophils, 0.3%; absolute eosinophil count, 1530/ml (normal 50–450/ml)]. His IgE was 2098 IU/ml (normal <200 IU/ml) and his haemoglobin was 9.9 mg/dl. About 6 months later, two subcutaneous nodules were found in his neck. Excisional biopsy was done which showed florid germinal centres, eosinophilic infiltration, eosinophilic abscesses and an increase of post-capillary venules—findings compatible with Kimura’s disease [2]. The patient’s cardiothoracic ratio (CTR) was 57.8%. Cardio-echography revealed dilatation of all four chambers with poor left ventricular performance [left ventricular ejection fraction (LVEF) 46%] and moderate pericardial effusion. Idiopathic dilated cardiomyopathy was diagnosed. The patient, however, refused pericardiocentesis or myocardial biopsy. We tried methylprednisolone 500 mg intravenously for 3 days then oral prednisolone 40 mg/day tapered to 10 mg/day for 6 months. His eosinophil count decreased from 3429 to 391/ml (from 34.5 to 6.1 as a percentage of WBCs). His CTR remained essentially unchanged (58.2%), and his left ventricular function did not improve (LVEF 45%) after 6 months of steroid treatment. Since then, the patient has not received steroids, because he has had no appreciable improvement of cardiac function. A systemic component is usually absent in Kimura’s disease, but the disease is often associated with proteinuria and nephrotic syndrome [3]. In our case, we could not identify the aetiology of idiopathic dilated cardiomyopathy because myocardial biopsy was not performed. We can, however, exclude dialysis-related cardiomyopathy, because the patient was well nourished and free from oedema, and he had the following laboratory parameters: creatinine clearance (Ccr), 73.82 l/week; weekly Kt/V, 2.46; and normalized protein catabolic rate (nPCR), 1.59 g/day. Based on a report by Sekiguchi et al., that steroid therapy was effective in 16 of 25 cases of eosinophilic heart disease [4], we tried steroids on this patient for 6 months, at the end of which his eosinophil count was decreased but without significant improvement of his left ventricular function. In conclusion, this is a unique case in which Kimura’s disease and idiopathic dilated cardiomyopathy co-existed. Their as yet undefined relationship may be evaluated further.

Fatal eosinophilic heart disease in a child with neurofibromatosis-1 complicated by acute lymphoblastic leukemia

We present a pediatric case of neurofibromatosis-1 (NF-1) complicated by acute lymphoblastic leukemia and hypereosinophilia, which caused multiple end-organ damage. Although clinical symptoms such as fever and coughing were noted only 1 week before admission, the condition deteriorated rapidly with a fatal outcome prior to antileukemic therapy. A postmortem examination demonstrated extensive endomyocardial fibrosis with thrombotic occlusion and recanalization of the coronary arteries. Leukemic cell infiltration was not seen in the cardiac tissue. When eosinophilia is diagnosed in patients with NF-1, eosinophilic end-organ damage, particularly cardiac involvement, in addition to hematological malignancies, should be screened for in order to start medical treatment at the early stage of the disease.

Eosinophilic heart disease with vasculitis: supported by HeartMate left ventricular assist device and heart transplantation

Eosinophilic heart disease is rarely seen in clinical practice. We report a patient with eosinophilic heart disease who presented with acute myocardial infarction and congestive heart failure. Because of lack of a donor organ and progressive deterioration of his general condition in spite of intraaortic balloon pumping, a left ventricular assist device (HeartMate 1000 IP; Thermo Cardiosystems Inc, Woburn, MA) was implanted before development of irreversible multiple organ failure and was followed by heart transplantation.

Helminth associated hypereosinophilia and tropical endomyocardial fibrosis (EMF) in Nigeria

There should be a recognisable trend between the incidence of hypereosinophilia and the duration of tropical endomyocardial fibrosis (EMF), if the hypothesis, that EMF is the burnt out phase of eosinophil associated heart disease, is correct. We tested this hypothesis in a prospective study of 89 consecutive EMF cases over an 18 year period at two Nigerian locations (Ife in South West and Calabar in South East). We carefully dated the duration of EMF symptoms at first presentation and screened for hypereosinophilia (eosinophilia≥1500/mm 3), and their causes. When no cause was identified for hypereosinophilia we gave a therapeutic trial with diethylcarbamazine to the patients. An eosinophil count≥1000/mm 3 was recorded in 80% of 24 cases seen within 6 months; 55% of 46 cases seen 0–24 months; 54% of 18 cases seen 25–48 months and 21% of 25 cases seen more than 49 months of onset of symptoms: while the respective distribution of eosinophil count≥1500/mm 3 for similar periods were 66, 44, 27 and 21%. This reflects a highly significant ( P<0.001) inverse relationship between hypereosinophilia and the duration of EMF and strengthens the concept that EMF (without eosinophilia) represents the late stage of eosinophilic heart disease. The localisation of endemic EMF to the low-lying tropical rain forest Zone and its predominant occurrence among rural dwellers and farmers suggest a vector borne etiologic agent. Microfilaria was the most likely cause of hypereosinophilia in the cases presented.

A case of allergic bronchopulmonary aspergillosis complicated with eosinophilic heart disease

A case of allergic bronchopulmonary aspergillosis complicated with eosinophilic heart disease

Clinicopathological study of eosinophilic heart disease

Clinicopathological study of eosinophilic heart disease

Eosinophil Peroxidase Levels in Hearts and Lungs of Mice Infected with Toxocara canis

Toxocara canis infection of abnormal hosts results in a condition in which infective larvae migrate through the soft tissues of the body, exclusive of the skin. This condition is known as visceral larva migrans (VLM) and causes a syndrome characterized by hepatosplenomegaly, hyperglobulinemia, hypereosinophilia, and transient pulmonary infiltrates. Because of the known association between hypereosinophilia and eosinophilic heart disease, we have been studying the hearts of mice infected with T. canis for evidence of myocardial damage and have previously described a severe eosinophilic myocarditis that leads to a marked myocardial fibrosis. We have measured eosinophil peroxidase (EPO) levels (a marker enzyme for specific granules of eosinophils) in homogenized lungs, homogenized hearts, and eosinophils recovered from the lungs of mice infected with T. canis over a 6-wk period. A marked accumulation of EPO was observed in the lungs of infected mice from day 14 postinfection (PI) to at least 6 wk of infection. Most of the EPO was associated with eosinophils that comprise the bulk of the pulmonary infiltrates associated with the VLM syndrome. However, following bronchoalveolar lavage, cytochemical localization of EPO activity in lungs from infected mice suggested that eosinophil degranulation had resulted in this marker enzyme being deposited within the pulmonary parenchyma. Peak levels of EPO were found in the myocardium by day 14 PI and declined over the 6-wk period. These levels equaled about 1/3 of the levels seen in the lungs of the same mice. These studies suggest that in mice infected with T. canis, the presence of increased numbers of eosinophils may lead to marked peroxidatic cardiopulmonary damage.

Familial restrictive cardiomyopathy with atrioventricular block and skeletal myopathy.

Five generations of an Italian family with an autosomal dominant restrictive cardiomyopathy are described. Members of four generations were examined. Symptoms usually developed in the third or fourth decade but the disease did occur in childhood. Initially the condition was characterised by normal ventricular size and systolic function with increased diastolic filling pressures in both ventricles and consequent bi-atrial enlargement. Cardiac catheterisation showed a left ventricular filling pattern of "dip and plateau". The electrocardiogram typically showed non-specific changes in the ST segment and T wave and changes indicating considerable atrial enlargement, which were confirmed by echocardiography. Light microscopy of two endocardial biopsy specimens showed no specific features but excluded the endomyocardial fibrosis of eosinophilic heart disease, amyloid, and specific heart muscle diseases. At necropsy in one case examined under light microscopy extensive patchy fibrosis was found throughout the endocardium, myocardium, and subepicardium, but there were no features typical of eosinophilic heart disease. Histopathological and biochemical examination of skeletal muscle identified no abnormality. The disease often had an insidious course over five to ten years after presentation. Bundle branch blocks, leading to complete atrioventricular block, however, often occurred and may be the first manifestation. Some individuals who survived into the fifth decade developed a progressive, non-wasting skeletal myopathy.

A case of eosinophilic heart disease diagnosed by endomyocardial biopsy findings.

A rare case of early stage eosinophilic heart disease was diagnosed by endomyocardial biopsy findings, despite the relatively low peripheral eosinophil blood count (640/mm3).

Clinical spectrum and endomyocardial biopsy findings in eosinophilic heart disease.

Fourteen cases of heart disease with hypereosinophilia were analyzed employing conventional cardiologic methods, including echocardiography, cardiac catheterization, and endomyocardial biopsy. The cases were divided into four types: Acute carditic (endocarditis, myocarditis, pericarditis; five cases); ventricular dilation (three cases); restrictive (three cases); electric disturbance (three cases). Biopsy revealed significant changes in all cases. In one case of the ventricular dilation type, endomyocardial fibrosis with myocardial degeneration was seen, and in another case mural thrombus formation was shown to be present. In three cases of the restrictive type, endomyocardial fibrosis (EMF) was observed. In two cases of the electric disturbance type, minor right ventricular myocardial degeneration was observed. In two of the three cases of the carditic type and in three of eight cases in other categories, postmyocarditic changes were observed. The course of the disease compared with the type of disorder revealed a short course in the carditic type and a longer course, ranging from 2 to 24 years, with one exception, in the other types. It is also confirmed that the various histopathologic changes can be related to particular clinical presentations. We have shown that the basic changes in eosinophilic heart disease are not restricted to the endomyocardium and that they occur in various parts of the heart causing more widespread manifestations. The more comprehensive term "eosinophilic heart disease" is a preferable description.