Cardio Case Challenge: A Confused 35-Year-Old With Headache, Fever, and Sore Chest

Priyanka Ghosh, DO; Saurabh Sharma, MD


June 01, 2022

The evaluation of myocarditis comprises a detailed history, including recent exposures, medications, any recent medication changes, and any allergies or asthma; a thorough physical examination; and laboratory studies, with basic blood tests, a complete blood cell count with differential, a comprehensive metabolic panel, cardiac biomarkers, and inflammatory markers. Cardiac imaging with TTE and cardiac MRI should be considered. Additionally, reactive causes of eosinophilia should be assessed. A definitive diagnosis is made through endomyocardial biopsy, although the sensitivity of the test is estimated at 50%, given the variable, sometimes focal nature of the disease.[5]

Upon histology, a characteristic pattern consists of mixed inflammatory cell infiltrates with a variable number of eosinophils within the myocardium. Unlike the hypersensitivity forms of eosinophilic myocarditis, hypereosinophilic syndromes are commonly associated with myocyte necrosis.[1]

The patient in this case presented with nonspecific symptoms that have a broad differential diagnosis, along with vague cardiac symptoms. His initially elevated temperatures raised suspicion for a possible infectious etiology. His physical examination, other than demonstrating an ill patient, provided no evidence of a possible source of infection. In the laboratory evaluation, his complete blood cell count was concerning, with a very elevated WBC count and a mildly decreased platelet count. His blood count differential was abnormal, with a significantly elevated percentage of eosinophils. Although increased peripheral eosinophilia can be due to multiple etiologies, the possible consequences of this finding must be considered. Markers such as the ESR and C-reactive protein level can be nonspecific; however, when elevated, they raise suspicion for an underlying inflammatory or malignant process.

The abnormal, elevated troponin cardiac biomarker, in addition to the ECG changes, indicated cardiac involvement in this patient, whether primary or secondary. The TTE was largely within normal limits. Although it was reassuring that no structural heart disease was found to explain his symptoms, the patient's presentation warranted ischemic evaluation with invasive coronary angiography. Results of the coronary angiogram, which showed no coronary artery disease, led to consideration of non-ischemic causes of the elevated troponin levels and ECG changes. The cardiac MRI scan was the next best step to evaluate the myocardium. Tissue characterization demonstrated large subendocardial and mid-myocardial areas of delayed enhancement, most prominent in the LV apex, in a pattern that suggested eosinophilic myocarditis or endomyocardial fibrosis. The imaging results were also suggestive of an LV apical thrombus, owing to the high (long) inversion recovery pulse sequence. This prompted a repeat TTE, which revealed abnormal layering echo density in the LV apex, confirming the presence of a thrombus.

Concurrent with the cardiac workup, an infectious disease workup was performed. Blood cultures and tests for acute viral illnesses were negative. The multiple blood cell line abnormalities prompted evaluation of the bone marrow with biopsy, which revealed the underlying etiology of this patient's eosinophilic myocarditis. The biopsy demonstrated increased blast cells and immunophenotypic findings that raised concern for acute leukemia with eosinophilia.

The differential diagnosis for this patient included other types of myocarditis, such as giant cell, viral, and hypersensitivity. Giant cell myocarditis is usually a rapidly progressive disease, in which the initial presentation is most commonly biventricular failure and ventricular tachycardia. An endomyocardial biopsy is the criterion standard for diagnosis. Viral myocarditis was ruled out in this patient, given the negative results on multiple viral studies and the higher likelihood of an eosinophilic etiology owing to his peripheral blood count abnormalities and underlying hematologic cancer. Hypersensitivity myocarditis is a subtype of eosinophilic myocarditis, which is associated with peripheral eosinophilia and is usually accompanied by an acute rash and fever. Most cases of hypersensitivity myocarditis have a temporal relation to recent initiation of a medication.

In this case, the patient's condition was stable upon presentation and he had not started any new medications before the onset of his symptoms, making giant cell and hypersensitivity myocarditis less likely. Although he did not undergo an endomyocardial biopsy, results from this procedure might have provided further evidence to differentiate his clinical condition from the others in the differential diagnosis.


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