Reversal of cardiac abnormalities in a young man with idiopathic hypereosinophilic syndrome using a tyrosine kinase inhibitor

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1 Eur J Echocardiography (2004) 5, 386e390 CASE REPORTS Reversal of cardiac abnormalities in a young man with idiopathic hypereosinophilic syndrome using a tyrosine kinase inhibitor Luigi Ascione a, ), Mario De Michele b, Maria Accadia a, Pasquale Spadaro a, Salvatore Rumolo a, Bernardino Tuccillo a a Division of Cardiology, S. Maria di Loreto Hospital, Viale dei Pini 4, Portici, Naples, Italy b Division of Cardiology, Moscati Hospital, Aversa, Italy Received 4 November 2003; received in revised form 19 February 2004; accepted 24 February 2004 KEYWORDS Echocardiography; Hypereosinophilic syndrome. Abstract We report a case of idiopathic hypereosinophilic syndrome in a young man, who showed symptoms and electrocardiographic findings mimicking an acute coronary syndrome. Two-dimensional echocardiography, together with laboratory data, allowed us to make the diagnosis and to start a treatment with imatinib mesylate, a 2-phenylamonopyrimidine-based tyrosine kinase inhibitor, which reversed the cardiac abnormalities. ª 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. Case report A 33-year-old man was admitted to the emergency department because of sudden onset of chest pain and shortness of breath at rest. On physical examination, he appeared diaphoretic with a blood pressure of 130/80 mmhg and a heart rate of 85 b/min. Cardiac auscultation revealed the presence of an olosystolic murmur and third heart sound at the apex, while crepitant rales were present in the mid and basal lung fields. The electrocardiogram showed sinus rhythm with ST segment elevation in V1eV3 precordial ) Corresponding author. Tel./fax: D address: luigi.ascione20@tin.it (L. Ascione). leads and ST segment depression in lateral leads (Fig. 1). On the basis of these data, a diagnosis of acute coronary syndrome was made and the patient was transferred to our coronary care unit. To better assess left ventricular function and to elucidate the cause of the olosystolic murmur, a transthoracic echocardiogram was performed with an ATL HDI-5000 CV digital system (Advanced Technology Laboratories, Bothell, U.S.A.) using a broad-band transducer with second harmonic capability (4e2 MHz). An apical long-axis view revealed normal left ventricular chamber size and function with obliteration of the apex by a large thrombus extending along the lateral wall to the posterior mitral leaflet that appeared, in a short-axis view, markedly limited in its motion /$30 ª 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. doi: /j.euje

2 Reversal of cardiac abnormalities in a young man 387 parasite serologies, IgE assessment, antinuclear antibodies and plasma cortisol evaluation. After such examinations and a bone marrow biopsy, a diagnosis of idiopathic hypereosinophilic syndrome was made. We decided to perform both a coronary angiography to confirm the absence of a significant coronary atherosclerosis and a percutaneous endomyocardial biopsy, but unfortunately, the patient refused to undergo an invasive assessment. A treatment with imatinib mesylate (400 mg/ die) and warfarin was started. After four months of this therapy, white blood cell count decreased to 7000/mm 3 (4% eosinophils), the electrocardiogram showed normal sinus rhythm without ST segment modifications (Fig. 3), and no thrombus both in the apex and along the posterobasal left ventricular wall was present at the echocardiographic examination (Fig. 4). Discussion Figure 1 ECG showing ST segment elevation in V1eV3 precordial leads and ST segment depression in lateral leads. (Fig. 2a,b). Color flow Doppler revealed a moderate mitral regurgitation with a jet impinging the lateral wall of the left atrium, while Pw-Doppler of mitral inflow showed a restrictive pattern with the E wave/a wave ratio >2 and a short deceleration time. Laboratory values were in the normal range, except for white blood cell count, which was of 24,000/mm 3 (70% eosinophils). The patient was treated with diuretics, digitalis and heparin and his conditions markedly improved within a few hours. On the second day, the patient was transferred to the hematology division. Chest radiography and abdominal and pelvic ultrasound scans were performed to rule out a neoplastic disorder. Furthermore, the patient underwent a wide range of laboratory tests, including stool cultures, Idiopathic hypereosinophilic syndrome is a term labelling clinical illnesses characterized by blood hypereosinophilia and widespread infiltration of organs and tissues by mature eosinophils. The diagnosis is based on the criteria of Chusid et al.: sustained eosinophilia (more than 1500 eosinophils per mm 3 ); the absence of other causes of eosinophilia, including parasitic infections and allergies; signs and symptoms of organ involvement. 1 The involvement of the myocardium occurs in more than half of the patients, may be right and/or left sided, and usually indicates worse prognosis. 2,3 Generally, the electrocardiogram shows non-specific ST segment and T wave abnormalities and arrhythmias, including atrial fibrillation and conduction defects. 4 A possible explanation for the unusual presentation in our young male relies on the fact that the eosinophil-mediated heart damage evolves through three stages: the acute necrotic stage, followed by the thrombotic stage which leads into the fibrotic stage. 5 The acute necrotic stage, marked by an intense myocarditis with an associated arteritis, could explain the patient chest pain and the presence of Q-waves in V1eV3 precordial leads with concomitant ST segment elevation. In our patient, two-dimensional echocardiographic findings, i.e. apical obliteration by echogenic endomyocardial proliferations extending along the posterolateral wall and involving the posterior mitral leaflet, with normal global and regional function was the clue for the diagnosis. Previously, Galiuto et al. reported a case of eosinophilic syndrome with an electrocardiographic presentation similar to a myocardial infarction,

3 Figure 2 (a) Apical long-axis view revealing a large thrombus extending along the lateral wall of the left ventricle; (b) the posterior mitral leaflet appeared markedly limited in its motion by the thrombus (parasternal short-axis view).

4 Reversal of cardiac abnormalities in a young man 389 Figure 3 ECG performed after four months of therapy with imatinib mesylate. Figure 4 Echocardiographic examination after four months of therapy, showing the absence of the thrombus.

5 390 L. Ascione et al. but with the echocardiographic finding of left ventricular dysfunction in conjunction with apical asynergy and thinning. 6 Recently, some cases of hypereosinophilic syndrome have been reported to respond to imatinib, a 2-phenylamonopyrimidine-based tyrosine kinase inhibitor, which has been approved for the treatment of BRCeABL positive chronic myeloid and acute lymphoblastic leukaemia. 7e10 The clinical condition and the hematologic features of our patient markedly improved after one month of this therapy and after four months no electrocardiographic and echocardiographic abnormalities could be observed. References 1. Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine 1975;54:1e Corssmit EP, Trip MD, Durrer JD. Loffler s endomyocarditis in the idiopathic hypereosinophilic syndrome. Cardiology 1999;91:272e6. 3. Parrillo JE. Heart disease and the eosinophil. N Engl J Med 1990;323:1560e1. 4. Spyrou N, Foale R. Restrictive cardiomyopathies. Curr Opin Cardiol 1994;9:344e8. 5. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood 1994;83:2759e Galiuto L, Enriquez-Sarano M, Reeder GS, Tezelar HD, Li ST, Millar Jr FA, et al. Eosinophilic myocarditis manifesting as myocardial infarction: early diagnosis and successful treatment. Mayo Clin Proc 1997;72:603e Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, et al. Efficacy and safety of a specific inhibitor of the BCReABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001;344:1031e7. 8. Druker BJ, Sawyers CL, Kantarjian H, Resta DS, Reese SF, Ford JM, et al. Activity of a specific inhibitor of the BRCe ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001;344: 1038e Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. Treatment of hypereosinophilic syndrome with imatinib mesylate. Lancet 2002;359:1577e Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201e14.