Cardiac Involvement in Hypereosinophilic Syndrome

Idiopathic Hypereosinophilic Syndrome

In 1975, Chusid and colleagues established diagnostic criteria for idiopathic HES (IHES) ( Box 155.1 ), substantially based on the finding of persistent hypereosinophilia (>1500/mm ³ for >6 months) with signs and symptoms of multisystemic organ dysfunction in the absence of other known causes of eosinophilia. Recent advances in the understanding of molecular pathogenesis of hypereosinophilia made it possible to distinguish two forms of IHES, according to the different mechanisms responsible for eosinophilia: myeloproliferative (M-HES) and lymphocytic (L-HES) variants of HES. The former has been related to genetic abnormalities leading to clonal expansion of the myeloid lineage, including eosinophils, subsequent to the activation of a tyrosine kinase. The latter has been associated to an overproduction of cytokines (interleukin-5 [IL]5]), stimulating growth of eosinophils, by abnormal circulating T cells.

In IHES, a variety of organs other than the heart are usually involved, including the lungs, bone marrow, and brain. Cardiac manifestations of IHES are frequent, involving 50% to 60% of the patients and represent the leading cause of morbidity and mortality. Particularly, heart failure, sudden death, and thromboembolism are the main cardiovascular manifestations, implying a worse prognosis and increased mortality rate. Cardiac damage is the result of myocardial infiltration with eosinophils or eosinophil-derived mediators, as confirmed by biopsy specimens revealing the presence of degranulated eosinophils and eosinophil cationic protein in the endocardium, as well as activated eosinophils at the myocardial interstitium. These mediators lead to endothelial damage and stimulate thrombus formation.

Secondary Hypereosinophilic Syndrome

The pathologic findings occur less commonly in patients with secondary hypereosinophilia related to parasitic disease, hypersensitivity, and tumor, although a smaller proportion of patients with such secondary hypereosinophilia manifest cardiac disease by two-dimensional echocardiography. As widely reported, typical cardiac findings include endocardial fibrosis and mural thrombosis, which is most frequent in the apices of both ventricles.

Clinical presentation depends on the stages of eosinophilic endomyocardial disease, which are as follows:

• 1.

  Necrotic stage, characterized by hypereosinophilia with systemic illness (20%–30%) and acute carditis (20%–50%)

• 2.

  Thrombotic stage with thromboemboli (10%–20%)

• 3.

  Fibrotic stage (late stage) with restrictive myopathy (10%) and valve regurgitations

To date, HES is included in the current classification of cardiomyopathies into the secondary forms.