Diagnosis and Outcome of Patients with Idiopathic Hypereosinophilic Syndrome and Cardiac Involvement

Introduction: Diagnostic criteria of idiopathic hypereosinophilic syndrome (iHES) comprise persisting reactive/non-clonal eosinophilia ≥1.5 G/l and associated organ infiltration/dysfunction. The pattern and extent of organ involvement is most relevant for symptoms, quality of life, complications, response to treatment and prognosis. Of note, the potentially life-threatening cardiac involvement (CI) is frequently underrecognized. Patients and Methods: Based on the ´German Registry on Disorders of Eosinophils and Mast Cells (GREM)', we sought to investigate CI in 62 patients (pts) with iHES and predominantly multifocal organ involvement (sinus [n=26], lungs [n=36, including asthma, n=23], abdominal organs [n=15], skin [n=15] and lymph nodes [n=9]) by cardiac magnetic resonance imaging (MRI, 62/62 pts), echocardiography (30/62 pts), myocardial biopsy (10/62 pts) and the cardiac biomarkers troponin I (TNI, 49/62 pts) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP, 38/62 pts). Clonal eosinophilia, e.g. FIP1L1::PDGFRA, alternative tyrosine kinase fusion genes and point mutations, e.g. KIT D816V, was excluded by the combination of cytogenetic/molecular analyses, bone marrow histology and immunohistochemistry. Myeloid peroxidase (MPO)-ANCA antibodies as characteristic marker of eosinophilic granulomatosis with polyangiitis (EGPA) were absent in all 62/62 (100%) pts and no evaluable patient had histologic evidence of vasculitis. Results: Cardiac MRI was pathologic in 34/62 (55%) pts with overlapping presence of late gadolinium enhancement (LGE, 31/34, 91%), pericardial effusion (11/34, 32%), involvement of heart valves/conduction system (9/34, 26%), impaired left-ventricular ejection fraction (LVEF