Clinical Review & Education
Challenges in Clinical Electrocardiography
Eosinophilia in a Man With Suspected
Acute Coronary Syndrome
Shannon Ruzycki, MD; Robert Jack Henry Miller, MD; Tyrone Harrison, MD
A man in his 60s presented with dull, right-sided shoulder pain of
12 hours’ duration relieved by nitroglycerin. He reported escalating
exertional chest discomfort with dyspnea over the preceding weeks.
Medical history included a provoked deep vein thrombosis and
chronic obstructive pulmonary disease. He took no new medica-
tions or supplements, and had not travelled significantly. Examina-
tion revealed an S4 heart sound at the apex and bilateral lower ex-
tremity edema. His high-sensitivity troponin-T level was 1365 ng/L
at presentation and 1310 ng/L at 6 hours (normal range, 0-14 ng/L).
Laboratory investigations were remarkable for an eosinophil level
of 78 000/μL (reference range, 0-7000 μL). His initial electrocar-
diogram (ECG) is shown in Figure 1. (To convert eosinophils to 109/L,
multiply by 0.001.)
Questions: What is the most likely cause of this patient’s chest
pain? What management course would you suggest?
Interpretation
The ECG shows sinus tachycardia with left axis deviation. There are
pathologic Q-waves in lead III and aVF, ST-T segment elevation in lead
III (1 mm) and aVF (0.5 mm), and ST-segment depression in leads I,
aVL, V5, and V6. The QRS duration is short (80 milliseconds [ms])
with borderline QTc prolongation at 455 ms (reference range, < 450
ms in males).
Figure 1. The 12-Lead Electrocardiogram of the Patient
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Clinical Course
Therapy for an acute coronary syndrome (ACS) was initiated. Trans-
thoracic echocardiography revealed a moderate-sized circumferen-
tial pericardial effusion without tamponade and moderate left ven-
tricular(LV)dysfunctionwithregionalvariability.Coronaryangiography
was unremarkable. Cardiac magnetic resonance imaging (Figure 2)
demonstrated extensive, patchy, late-gadolinium enhancement (LGE)
consistent with myocarditis. There was also a prominent subendo-
cardial distribution suggesting possible coronary vasculitis. Bone mar-
row aspiration demonstrated hypercellular marrow with prominent
infiltration of eosinophils with negative flow cytometry.
High-dose intravenous methylprednisone was administered
with rapid reduction in eosinophilia. Following a 3-month course of
tapering oral prednisone, repeat echocardiography showed recov-
ery of LV function.
Discussion
Eosinophilic myocarditis is a rare disease. Eosinophil infiltration leads
to degranulation, inflammation, and eventual necrosis and
apoptosis.1 Most patients have peripheral eosinophilia.2 Causes in-
clude hypersensitivity reaction to medications or parasite infec-
tions, hematologic malignancies, autoimmune disease, or primary
hypereosinophilic syndrome (HES).3
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 Clinical Review & Education Challenges in Clinical Electrocardiography
Figure 2. Cardiac Magnetic Resonance Imaging
A Short-axis view B Long-axis view
Clinical manifestations of eosinophilic myocarditis range from
mild to life-threatening.3,4 Nonspecific symptoms like syncope, chest
discomfort, palpitations, and fatigue are common.2,3 Patients may
have chronic, subacute, or fulminant heart failure.2,4 Not uncom-
monly, patients present with chest discomfort and ST-T segment ab-
normalities mimicking ACS.2,3,5 Cardiac biomarkers are usually
elevated.3 Occasionally, patients present with cardiogenic shock and
sudden cardiac death.1,2,4
The ECG features in eosinophilic myocarditis are likewise non-
specific. Heart block, ventricular tachycardia, bundle branch block, T-
wave inversion, and ST-T segment abnormalities are reported.2-5 The
presenting ECG findings can be used for prognostication; QTc greater
than 440 ms and QRS duration greater than 120 ms confer worse clini-
cal outcomes.6 Left bundle branch block and pathologic Q-waves are
associated with higher rates of death or transplantation.7
The progressive chest pain in our patient was compatible
with both myocardial infarction or myocarditis. The elevated but
stable troponin is more suggestive of myocardial inflammation
than progressive myocyte death, in which a troponin rise would
be expected. The ST-segment elevation correlated with the loca-
tion of LGE on cardiac magnetic resonance imaging, and the
pathologic Q-waves were associated with transmural LGE.8 This
may have been secondary to eosinophilic inflammation or coro-
nary artery vasculitis.
A high index of suspicion is required to consider eosinophilic
myocarditis. Peripheral eosinophils greater than 1.5 × 109/L is
suggestive. Taking a careful history may illicit a potential precipi-
tant; identification of all medications, over-the-counter drugs,
and nonpharmaceutical supplements taken is critical.4 Investiga-
tion for parasites and autoimmune disease may be warranted.
Bone marrow biopsy may be necessary if no precipitant is identi-
fied. The diagnostic gold standard is endomyocardial biopsy; this
may be unnecessary if other features are highly suggestive of
eosinophilic myocarditis.2,4
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A, Short-axis view. B, Four-chamber
view of delayed enhancement
sequences. There is a moderate
pericardial effusion (yellow
arrowheads) as well as mid-wall
(black arrowhead) and
subendocardial (white arrowheads)
late gadolinium enhancement.
Cardiac magnetic resonance imaging may reveal features of
myocarditis, such as myocardial edema and diffuse myocardial LGE.5
In eosinophilic myocarditis, the LGE typically occurs in mid-wall
regions.9 Eosinophilic endomyocardial fibrosis is associated with dif-
fuse subendocardial LGE and obliteration of the LV apex with fi-
brous tissue.9 Our case demonstrated both distributions; however,
the lack of apical involvement suggests that the subendocardial LGE
may have been related to concurrent coronary vasculitis. In addi-
tion, the LGE spanned several coronary distributions further argu-
ing against a diagnosis of ACS.
Treatmentforeosinophilicmyocarditisisbasedonexpertopinion.3
Implicated drugs must be discontinued. Secondary causes should be
treated. Prompt corticosteroid therapy is critical to prevent end-organ
damage.3,4 Optimal treatment duration is unknown; greater than
6 months is standard, although a longer period of time may be
warranted.2 Therapeutic response is varied; a subset of patients rap-
idlyrecovermyocardialfunctionwithcorticosteroids.3,4 Otherpatients
rapidly decline despite aggressive immunosuppression.1 Relapse af-
ter cessation of therapy has been reported.1
Hypereosinophilic syndrome is a disorder of sustained
eosinophil production (> 1.5 × 109/L for 6 months) with infiltra-
tion and damage of tissues.10 When no underlying hematologic
malignant neoplasm, infection, or autoimmune disease is found,
the term idiopathic HES is used.10 Most patients with HES have
cardiac involvement at presentation, which is the most common
cause of death. 1,10 Treatment includes steroids, aggressive
immune suppression, and bone marrow transplantation in refrac-
tory cases.10
Take-Home Points
• Complete evaluation of patients presenting with possible ACS
should include attention to all abnormal laboratory values.
• Eosinophilic myocarditis can present with a wide range of clinical
features and may mimic ACS.
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 Challenges in Clinical Electrocardiography Clinical Review & Education

• Evaluation for the underlying cause of eosinophilia includes his- • The gold standard for diagnosis is endomyocardial biopsy.
tory, physical examination, and investigations for new medica- • Treatment for eosinophilic myocarditis is not standardized but typi-
tions, parasite infection, autoimmune disease, and hematologic ma- cally includes therapy directed at the underlying cause and immu-
lignancy nosuppression.

ARTICLE INFORMATION
Author Affiliations: Department of Medicine,
University of Calgary, Calgary, Alberta, Canada
(Ruzycki, Miller, Harrison); Libin Cardiovascular
Institute of Alberta, Calgary, Alberta, Canada
(Miller).
Corresponding Author: Shannon Ruzycki, MD,
Department of Medicine, University of Calgary,
1820 Richmond Rd SW, Room 18126 RRDTC,
Calgary, AB T2T 5C7, Canada (sarro@ualberta.ca).
Section Editors: Zachary D. Goldberger, MD, MS;
Nora Goldschlager, MD; Elsayed Z. Soliman, MD,
MSc, MS.
Published Online: September 26, 2016.
doi:10.1001/jamainternmed.2016.5781
Conflict of Interest Disclosures: None reported.
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