Eosinophilic myocarditis is a unique cause of myocarditis, usually presenting progressive heart deterioration and evidence of eosinophilia.1 It may be secondary to leukemia, parasite infection, allergic disease, granumatous disease, connective tissue disease, vasculitis such as Churg-Strauss syndrome, or primary hypereosinophilic syndrome.2 The clinical picture ranges from asymptomatic endocardial infiltration and fulminate myocarditis to chronic restrictive cardiomyopathy with or without apical thrombus formation. Initially, the eosinophil infiltration produces endomyocardial necrosis, inflammation and arteritis, representing acute necrotizing eosinophilic myocarditis. Then, the second thrombotic phase and chronic endomyocardial fibrosis subsequently follow.3 Definite diagnosis is based on endomyocardial biopsy; however, unique echocardiographic picture with eosinophilia is essentially diagnostic.4
2. Case report
A 24-year-old Filipino woman was admitted due to fever and back soreness for several days. There was no symptom or sign related to heart failure at admission. Dry cough, orthopnea, and leg edema were first noted and progressing since the second day of admission. Acute pulmonary edema was also evident in the chest film and rapidly progressed to respiratory failure. She was intubated on the third day. New systolic murmur at apex was heard during auscultation. Blood tests showed leukocytosis of 75.8×109/L (normal range 4–10×109/L), profound eosinophilia of 60.64×109/L (normal range 50–350×109/L), elevated cardiac enzymes including creatine kinase (CK; 914U/L, normal range <160U/L), CK-MB (17U/L, normal range <16U/L), and troponin-I (10.3ng/ml, normal range <0.034U/L). The patient's electrocardiogram (ECG) revealed low voltage in limb leads and poor R-wave progression in precordial leads. Pulmonary artery wedge pressure was 39mmHg, and the cardiac index was 4.42L/min/m2 under inotropic agent support. Transthoracic echocardiogram (TTE) showed an unusual thickening and high echogenicity of the endocardium, which was asymmetrically distributed at the basal part of the posterior wall and lateral wall of the left ventricle (LV). The anterior wall of the LV, the interventricular septum and the right ventricle (RV) were relatively spared. The posterior leaflet of the mitral valve was also involved, resulting in moderate eccentric mitral regurgitation. Pulse-wave Doppler imaging of mitral inflow demonstrated that the ratio of E wave to A wave was high and the deceleration time was short. The restrictive mitral inflow pattern suggested severe diastolic dysfunction (Fig. 1). The chamber sizes were normal, and the LV systolic function was preserved. There was no thrombus at the apex of the LV or RV. By profound eosinophilia and the unique echocardiographic picture, acute necrotizing eosinophilic myocarditis was diagnosed.
Intensive chemotherapy including high-dose steroid and antibiotics were prescribed soon after acute lymphoblastic leukemia was diagnosed by bone marrow biopsy. Hemodynamics was supported by inotropic agent. The patient survived after neutropenic sepsis following chemotherapy, and was discharged in 2 months.
Eosinophilia, which is caused by many diseases, can involve multiple organs,5 including the heart, characterized as eosinophilic cardiomyopathy.6 It was first discovered in 1936 by Löffler and called “fibroplastic parietal endocarditis with blood eosinophilia”. Heart involvement usually happens in eosinophil counts exceeding 1.5×109/L for at least 6 months.3 As described by Löffler, the subacute and chronic forms of eosinophilic myocarditis, characterized by variable degree of fibrosis and thrombosis and chronically progressive heart failure, are more well-known. Cytotoxic agents and corticosteroid may improve outcome in these patients.7 In contrast, acute necrotizing eosinophilic endocarditis, the initial presentation of eosinophilic myocarditis, is extremely rare and is always fatal as a medical emergency.8 Eosinophil infiltration and degranuation causing profound necrosis and arteritis are the hallmarks in the disease.9 No effective treatment is proven yet. Cardiac support and treating the underlying disease is generally considered.
The hallmarks of echocardiography of eosinophilic myocarditis are endocardial infiltration, apical thrombus formation and endocardial fibrosis as the disease progresses.10 The geometrics of heart involvement is uniquely confined to the LV basal segment of the posterior wall, and further impairs the motion of the posterior mitral leaflet to cause eccentric mitral regurgitation. Diastolic dysfunction is always seen, and restrictive cardiomyopathy is evident in the chronic stage. The image of eosinophilic myocarditis in the chronic stage is well documented, characterized by the obliteration of the apex in RV or LV by thrombosis and fibrosis.2 However, reports in the literature of acute necrotizing eosinophilic endocarditis are extremely rare. In our case, the endocardium of RV and interventricular septum were spared, and LV endocardial biopsy in the hemodynamically unstable patient was very risky. Noninvasive TTE showed a specific and typical picture without thrombus or fibrosis. Combined with the rapidly progressive cardiac course and systemic eosinophilia, the diagnosis of acute necrotizing eosinophilic cardiomyopathy is convincing without endomyocardial biopsy.
No randomized controlled trial has yet evaluated the treatment of eosinophilic myocarditis. Some observational trials reported that high-dose steroid and cytotoxic agents may be beneficial.11 The experience of treating acute necrotizing eosinophilic cardiomopathy is more limited. The therapy is usually focused on cardiac support and the underlying etiology of eosinophilia. Some literature reported dramatic improvement after steroid treatment.12 However, due to the rapidly progressive course and diagnostic difficulty, many patients were diagnosed by autopsy without prompt treatment before their death. Quick and correct diagnosis is essential to treat the disease and prevent fatality, but is rarely achieved. Thus, endocardial biopsy should not be delayed if the imaging is not diagnostic with clinical suspicion.13 In our patient, typical echocardiography provided precise diagnosis in a noninvasive manner, and made the strong link between clinical heart failure and acute lymphoblastic leukemia-related eosinophilia. It was also an important guide for the therapy in the initially fulminant course.
In conclusion, acute necrotizing eosinophilic myocarditis is extremely rare, with poor prognosis. It should be suspected in all patients with eosinophilia and unexplained heart failure, especially with a rapidly progressive course. To identify the unique echocardiographic picture helps produce the diagnosis early and may improve outcome. The case we have presented showed a typical clinical course and specific imaging. Although rare, the echocardiographic image brought a strong clue to the diagnosis and lead to successful treatment in our case.
This study was supported in part by the National Science Council Grants, 98-2314-B-075A-010-33-MY2, 98-2314-B-075A-011-MY2, Taipei, Taiwan, and by the Yen Tjing Ling Medical Foundation (CI-97-12), Taipei, Taiwan, ROC.
1. Cooper LT Jr. Myocarditis. N Engl J Med
2. Ommen SR, Seward JB, Tajik AJ. Clinical and echocardiographic features of hypereosinophilic syndromes. Am J Cardiol
3. Herzog CA, Snover DC, Staley NA. Acute necrotising eosinophilic myocarditis
. Br Heart J
4. Sen T, Gungor O, Akpinar I, Cetin M, Tufekcioglu O, Golbasi Z. Cardiac involvement in hypereosinophilic syndrome. Tex Heart Inst J
5. Liu KT, Wu MH, Chiu CH, Tung SM, Wu YJ, Chang SC. Idiopathic acute eosinophilic pneumonia. J Chin Med Assoc
6. Brito-Babapulle F. The eosinophilias, including the idiopathic hypereosinophilic syndrome. Br J Haematol
7. Ginsberg F, Parrillo JE. Eosinophilic myocarditis
. Heart Fail Clin
8. Cooper LT, Zehr KJ. Biventricular assist device placement and immunosuppression as therapy for necrotizing eosinophilic myocarditis
. Nat Clin Pract Cardiovasc Med
9. deMello DE, Liapis H, Jureidini S, Nouri S, Kephart GM, Gleich GJ. Cardiac localization of eosinophil-granule major basic protein in acute necrotizing myocarditis. N Engl J Med
10. Shah R, Ananthasubramaniam K. Evaluation of cardiac involvement in hypereosinophilic syndrome: complementary roles of transthoracic, transesophageal, and contrast echocardiography. Echocardiography
11. Thambidorai SK, Korlakunta HL, Arouni AJ, Hunter WJ, Holmberg MJ. Acute eosinophilic myocarditis
mimicking myocardial infarction. Tex Heart Inst J
12. Adsett M, West MJ, Galbraith A, Duhig E, Lange A, Palka P. Eosinophilic heart: marked left ventricular wall thickening and myocardial dysfunction improving with corticosteroid therapy. Echocardiography
13. Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology. Endorsed by the Heart failure society of America and the Heart Failure Association of the European Society of Cardiology. J Am Coll Cardiol