Eosinophilic myocarditis: diagnostic pitfalls and therapeutic challenges. A Case Series

Background Eosinophilic myocarditis (EM) is a rare and potentially life-threatening inflammatory heart disease. Diagnosis is frequently delayed because clinical presentations are heterogeneous, early cardiovascular magnetic resonance (CMR) lacks a pathognomonic pattern, and endomyocardial biopsy (EMB) is often performed late or after glucocorticoid exposure. A further pitfall is assuming that EM can be excluded in the absence of peripheral eosinophilia or overt extracardiac disease. Delayed recognition may result in irreversible myocardial injury, endomyocardial fibrosis and adverse clinical outcomes. Case summary We report four cases of EM managed at our institution, each exemplifying a distinct diagnostic and therapeutic challenge. The first case was initially misclassified as apical hypertrophic cardiomyopathy on transthoracic echocardiography and CMR due to apical pseudo-hypertrophy, later evolving into endomyocardial fibrosis with severe mitral regurgitation requiring surgical annuloplasty, without clinical evidence of systemic disease. The second case was consistent with anti-neutrophil cytoplasmic antibodies (ANCA)-negative EGPA complicated by myocarditis; prolonged glucocorticoid exposure likely attenuated peripheral eosinophilia and masked eosinophils on EMB. The third case was initially classified as lymphocytic myocarditis based on an EMB performed under glucocorticoids, with eosinophilic infiltration and Loeffler endocarditis uncovered on repeat biopsy after steroid tapering. The fourth case presented with ST-segment elevation myocardial infarction secondary to coronary embolism in the setting of idiopathic hypereosinophilia. Across cases, we detail the diagnostic workup, emphasizing the complementary role of multimodality imaging and EMB, and outline therapeutic strategies, combining conventional immunosuppression with emerging targeted therapies against the interleukin-5 pathway. Conclusions EM may present as an isolated, organ-specific cardiac disease in the absence of extracardiac involvement or peripheral eosinophilia, with a time-dependent prognosis. Diagnostic pitfalls frequently arise from reliance on non-invasive imaging alone and from smoldering disease course, particularly when chronic glucocorticoid therapy masks both clinical and histological features. Clinicians should maintain a high level of suspicion for EM diagnosis, even in absence of peripheral hypereosinophilia and if endomyocardial biopsy is obtained after acute or chronic steroid therapy, and consider possible thromboembolic complications, such as coronary artery embolization.