Journal of Veterinary Cardiology (2016) -, -e-

www.elsevier.com/locate/jvc

A case of an unexplained eosinophilic

myocarditis in a dog*
T.P. Keeshen, DVM a,*, M. Chalkley, BSc, BVSc (Hons),
MANZCVSc (Pathobiology), DACVP b, C. Stauthammer, DVM,
DACVIM-Cardiology c

a
University of Minnesota, College of Veterinary Medicine, United States
b
University of Minnesota, Veterinary Diagnostic Laboratory, Pathology Department,
United States
c
University of Minnesota, College of Veterinary Medicine, Cardiology Department

Received 30 April 2015; received in revised form 5 March 2016; accepted 18 March 2016

KEYWORDS Abstract An 8-year-old spayed female Munsterlander was evaluated for a chronic
Canine; low grade fever and a two month history of exercise intolerance. On physical ex-
Cardiac infiltrate; amination, tachycardia and a grade II/VI right systolic heart murmur were de-
Eosinophilia; tected. Echocardiography revealed marked thickening of the atrial and
Hypereosinophilic ventricular walls with mixed echogenicity and concentric hypertrophy of the left
syndrome and right ventricles and equivocal systolic dysfunction. Serum cardiac troponin I le-
vel was markedly elevated. Endomyocardial biopsy was attempted; however, the
patient arrested during the procedure and resuscitation was unsuccessful. Post-
mortem examination revealed severe, chronic atrial and ventricular eosinophilic
myocarditis associated with marked interstitial fibrosis. Serological testing, histo-
pathology and immunohistochemistry staining did not reveal an underlying infec-
tious agent or neoplasm. To our knowledge, this is the first reported case of

*
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* Corresponding author.
E-mail address: tkeeshen@ufl.edu (T.P. Keeshen).

http://dx.doi.org/10.1016/j.jvc.2016.03.001
1760-2734/Published by Elsevier B.V.

Please cite this article in press as: Keeshen TP, et al., A case of an unexplained eosinophilic myocarditis in a dog, Journal of
Veterinary Cardiology (2016), http://dx.doi.org/10.1016/j.jvc.2016.03.001
2 T.P. Keeshen et al.
primary eosinophilic myocarditis in the absence of a peripheral eosinophilia and
multi-organ eosinophilic inflammation in a dog.
Published by Elsevier B.V.
An 8-year-old spayed female Munsterlander
weighing 23.8 kg was referred to the University of
Minnesota Veterinary Medical Center for evaluation
of a one month history of low grade fever ranging
from 102.6 to 103.0 F (39.2e39.4  C) and a two
month history of exercise intolerance. The symp-
toms were characterized by frequent breaks during
walks, reluctance to perform tricks, and inter-
mittent thoracic limb weakness. The dog presented
to its regular veterinarian one month before eval-
uation with a normal physical examination other
than the fever and an elevated alanine trans-
aminase value of 284 U/L (range 10e118 U/L).
Additional diagnostics were declined by the owners,
and the patient was prescribed doxycycline
(7.7 mg/kg [3.5 mg/lbs] q12 h). The clinical signs
and fever did not improve with treatment and the
doxycycline was subsequently discontinued after
three weeks. The patient had no history of travel
outside of Northern Midwest USA.
On physical examination, tachycardia with a
heart rate of 200 beats per minute with synchronous
femoral pulses and a grade II/VI right systolic mur-
mur were noted. The patient was markedly
depressed and lethargic and had a low grade fever
of 102.6 F. complete blood count revealed
increased neutrophils at 12.11  10^3/uL (range
2.1e11.2  10^3/uL), decreased lymphocytes at
0.58  10^3/uL (range 0.78e3.36  10^3/uL), and a
normal number of eosinophils at 0.87  10^3/uL
(range 0.0e1.2  10^3/uL). Serum biochemistry
analysis revealed an elevated creatine kinase at
2398 U/L (range 36e348 U/L), alanine transferase
at 139 U/L (range 22e92 U/L), and aspartate
transferase at 158 U/L (range 16e44 U/L). Uri-
nalysis was unremarkable. SNAP 4DX Plus Test
(Idexx) was negative for Dirofilaria immitis, Ana-
plasma spp., Ehrlichia spp., and Borrelia burgdor-
feri. Urine blastomycosis antigen testing and
Toxoplasma serology were also negative. Systolic
blood pressure was considered normal at
130 mmHg. ECG revealed a sinus tachycardia with a
heart rate of 200 BPM and left bundle branch block.
A transthoracic echocardiographic study was
performed using a 4e2 MHz phased-array trans-
ducer. The interventricular septum and left and
right ventricular free walls were markedly
increased in thickness. The myocardium within the
thickened walls was mottled with mixed echoge-
nicity in conjunction with subendocardial
Please cite this article in press as: Keeshen TP, et al., A case of an unexplained eosinophilic myocarditis in a dog, Journal of
Veterinary Cardiology (2016), http://dx.doi.org/10.1016/j.jvc.2016.03.001
myocardial hyperechogenicity and subepicardial
hypoechogenicity (Fig. 1A, Videos 1 and 2). Systolic
left ventricular wall motion appeared diminished
globally. The myocardium of the right atrium and
auricle was also severely thickened and irregular
with an echogenicity similar to the ventricles
(Fig. 1B, Video 3). The left ventricular chamber
diameter on M-mode was diminished in size during
diastole (2.7 cm; range 3.3e4.8 cm) and systole
(2.0 cm; range 2.0e3.5 cm) with a low normal
fractional shortening value of 25%. The left atrial
dimension appeared subjectively normal relative to
the aorta and measured within reference range on
M-mode at 2.3 cm (range 1.8e2.9 cm). Mitral inflow
profiles were summated secondary to the patient’s
heart rate. There was a mild amount of effusion
present within the pericardium. Serum cardiac
Troponin-Id was measured due to the above echo-
cardiographic findings and was markedly elevated
at 20.9 ng/mL (range <0.03 mg/dL).
Based on the clinical suspicion of an infiltrative
inflammatory or neoplastic disease of the myocar-
dium, an endomyocardial biopsy was recom-
mended. The patient was induced with intravenous
diazepam (0.1 mg/kg) and etomidate (1 mg/kg)
following premedication with morphine (0.5 mg/kg)
and maintained on inhaled sevoflurane. The right
jugular vein was isolated via a cut down, and a 10 Fr
Vascular access sheathe was inserted into the ves-
sel. A 7 Fr sheath with dilatorf in place was then
directed into the right atrium under fluoroscopic
guidance. A number 18 bronchoscopic biopsy for-
cepsg were then inserted into the sheath lumen
after removal of the dilator. As the biopsy forceps
were moved adjacent to the myocardium within the
right ventricular apex, the patient underwent car-
diopulmonary arrest characterized by pulseless
electrical activity with a normal sinus rhythm seen
on electrocardiogram. Cardiopulmonary resuscita-
tion was immediately performed; however the
patient was unable to be revived.
The dog was subsequently submitted to Uni-
versity of Minnesota Veterinary Diagnostic Labo-
ratory for post-mortem examination. The most
d
Advia Centaur CP Ultra-TnI, Erlangen Germany.
e
Percutaneous Sheath Introducer Set, Arrow International
Inc., Reading, PA.
f
Flexor Check Flo Cook, Bloomington IN.
g
Olympus Biopsy Forceps, Olympus Japan.
Unexplained eosinophilic myocarditis in a dog 3

Figure 1 A: Right parasternal four chamber echocardiographic image recorded at mid-diastole demonstrating
marked ventricular wall thickening of mixed echogenicity. B: Echocardiographic image from a left cranial view of the
right atrium and auricle demonstrating marked thickening of the atrial wall of similar echogenicity as noted within the
ventricular myocardium.

significant post-mortem finding was marked thick-
ening with white and tan mottling of the atrial and
ventricular myocardium (Fig. 2). The epicardium
displayed numerous, variably sized, multifocal to
coalescing, tan pink, slightly raised areas of dis-
coloration. Expanding the myocardium and elevat-
ing the endocardium of the right atrium were
multiple raised, smooth, dark red and tan, moder-
ately firm nodules (Fig. 3). There was mild hemo-
pericardium and the heart was moderately
enlarged and weighed 308 g; 1.3% of the body
weight (normal 0.85e1% body weight). There was
no evidence of myocardial perforation from the
biopsy forceps. Representative samples from vari-
ous organs and tissues were harvested for histo-
pathology. Microscopically, there were numerous,
interconnecting, broad bands of pleocellular,
myocardial inflammatory infiltrates accompanied
by marked interstitial to replacement fibrosis
within the ventricular walls, and similar, multifocal
nodular inflammatory infiltrates and fibrosis
expanding the atrial endocardium and myocardium
(Fig. 4A). The pleocellular inflammatory infiltrates
predominantly comprised mature eosinophils, with
lesser infiltrates of macrophages, mast cells, small
mature lymphocytes and plasma cells (Fig. 4B).
There was marked cardiomyofiber atrophy and loss
within the inflammatory/fibrotic regions. Histo-
pathological examination of other organs and tis-
sues did not reveal any significant lesions.

Figure 3 Gross cross section taken from the apical

aspect of the left and right atria. Multiple raised,
Figure 2 Cross section views of the left ventricle dem- smooth, dark red to tan nodules are evident on the
onstrating the tan discoloration throughout the myocar- endocardial surface of the right atrium located on the
dium. The endocardium appears largely unaffected. left hand side of the image.

Please cite this article in press as: Keeshen TP, et al., A case of an unexplained eosinophilic myocarditis in a dog, Journal of
Veterinary Cardiology (2016), http://dx.doi.org/10.1016/j.jvc.2016.03.001
4 T.P. Keeshen et al.

Figure 4 A: Low power microscopic image of the left ventricle demonstrating numerous, interconnecting, broad
bands of pleocellular myocardial inflammatory infiltrates accompanied by marked interstitial fibrosis. B: High power
microscopic image of the left ventricle demonstrating a pleocellular inflammatory infiltrate predominantly comprised
of mature eosinophils, with lesser infiltrates of macrophages, mast cells, small mature lymphocytes and plasma cells.

Infectious agents including, but not limited to,
bacteria, fungi, intra-cellular and extra-cellular
protozoa and parasitic elements were not evident
on extensive examination of routinely stained rep-
resentative sections of multiple organs and tissues,
including the heart. Special stains including Gram
stain, acid-fast stain, Periodic Acid-Schiff, and
Grocott’s Methenamine Silver and Giemsa stains
were negative for bacteria, mycobacterial species,
fungal elements, prototheca and protozoa. Immu-
nohistochemical markers for T-lymphocytes, B-
lymphocytes and mast cells failed to reveal an
emergent round cell neoplastic population within
the inflammatory infiltrates. Immunohistochemis-
try for Neospora caninum, Toxoplasma gondii, and
Sarcocystis neurona did not reveal any immunor-
eactive infectious elements.
Discussion
This was a unique case of eosinophilic myocarditis.
To our knowledge, there have been no reported
cases of eosinophilic myocarditis affecting dogs in
the absence of a recognizable infectious etio-
logical agent, multi-organ eosinophilic inflamma-
tion and/or peripheral eosinophilia. There are
certain diseases such as eosinophilic leukemia and
hypereosinophilic syndrome (HES) wherein eosi-
nophils infiltrate multiple organs and are asso-
ciated with a peripheral eosinophilia; however
these are more common in cats and very rare in
dogs.1,2 HES is a condition described in people and
animals where eosinophils infiltrate into organs
leading to damage of the tissues and the under-
lying cause is not found.1 Eosinophilic inflamma-
tion may occur in association with an allergic or
hypersensitivity reaction (drug or non-drug
induced), parasitic infection (e.g. heartworm dis-
ease, Toxocariasis, Toxoplasma gondii, Neospora
caninum and Sarcocystis spp.), fungi and proto-
theca, paraneoplastic syndrome (most commonly
mast cell tumor/mastocytosis and T-lymphoma),
granulocytic leukemia, and HES.1 The common
feature of most of these conditions is concurrent
peripheral eosinophilia.1 In contrast, peripheral
eosinophils were within the normal reference
range in the present case and eosinophils were
exclusively confined to the heart.
Protozoal infections including Sarcocystis spp.,
Toxoplasma gondii, and Neospora spp., frequently
induce eosinophilic inflammation in tissues such as
the brain, eyes, heart, liver, and skeletal muscle.3
Common species infected by these protozoa are
opossums, cats, marine mammals, and horses; dogs
are uncommonly affected.3 In cattle, Sarcocystis
spp. are commonly associated with bovine eosino-
philic myositis, a condition characterized by eosi-
nophilic infiltrates within skeletal muscle,
diaphragm, tongue, heart, and esophagus.4 Similar
cardiac gross and histopathological changes to those
observed in bovine eosinophilic myositis were pres-
ent in the current case, however, no parasitic ele-
ments were seen on any histological examination of
the tissue from this patient.4 Pythium insidiosum is
an infectious fungal-like disease that can infect
humans and animals.5 This disease can also cause
massive accumulation of eosinophils within infected
tissues.5 The diagnosis is usually reliant on histo-
logical detection of large branching hyphae.5 In the
present case, thorough investigation of
routinely and specially stained histological sections
did not reveal any infectious agents in any tissue,
including heart, skeletal muscle, and diaphragm.

Please cite this article in press as: Keeshen TP, et al., A case of an unexplained eosinophilic myocarditis in a dog, Journal of
Veterinary Cardiology (2016), http://dx.doi.org/10.1016/j.jvc.2016.03.001
Unexplained eosinophilic myocarditis in a dog
A previous case report in a dog described a vis-
ceral mast cell tumor causing hypereosinophilia and
eosinophilic inflammation of secondary organs;
including the liver, spleen, duodenum, mediastinal
lymph nodes, and heart.6 This specific case had
evidence of myocarditis, necrosis, and fibrosis along
with an elevated serum troponin concentration.6
The authors characterized this as Loeffler’s endo-
carditis according to the criteria described in people
as having myocarditis based on echocardiography or
MRI imaging and hypereosinophilia.7 This is a case
where the neoplastic mast cells caused a hyper-
eosinophilia leading to the changes seen post-
mortem within other organs.6 In contrast, the cur-
rent case of myocarditis was not associated with
hypereosinophilia; there was no evidence of neo-
plastic mast cells in any of the tissues examined
microscopically and the inflammatory infiltrates
were isolated to the cardiac tissue with no involve-
ment of other internal organs.
The patient in the present case had no history of
hypersensitivity to any drugs or administration of
drugs before initiation of clinical signs. The dog
was placed on doxycycline; however this occurred
after the development of clinical signs. Churge-
Strauss syndrome is a very rare disease in people
characterized by systemic vasculitis, eosinophilic
infiltration, and peripheral eosinophilia.8 This
condition has never been described in veterinary
patients and does not fit the clinical picture with
this patient. With no clear infectious cause found
with the samples submitted and the tests run on
this patient, we are left to conclude that this is a
case of idiopathic eosinophilic endomyocarditis. It
is impossible to determine if necrosis and fibrosis
of the myocardium led to eosinophilic infiltration,
or alternatively, if eosinophilic infiltration caused
the necrosis and fibrosis.
The human medical literature has reported less
than 30 cases of primary eosinophilic myocarditis.9
Eosinophilic myocarditis can be caused by distinct
mechanisms of myocardial inflammation.9 They
include infectious myocarditis, allergic/hyper-
sensitivity reaction to certain drugs, systemic dis-
orders such as ChurgeStrauss syndrome, some forms
of idiopathic restrictive myocarditis, idiopathic
eosinophilic myocarditis or secondary to acute ful-
minating necrotic myocarditis.9 These conditions
are usually associated with a peripheral eosino-
philia. The clinicopathological presentation in this
case, particularly the absence of recognized infec-
tious causes of eosinophilic inflammation, neo-
plastic disease and eosinophilia, most closely
resembles that of idiopathic eosinophilic myocardi-
tis in human beings, a rare subtype of myocarditis
characterized by focal to diffuse eosinophilic
Please cite this article in press as: Keeshen TP, et al., A case of an unexplained eosinophilic myocarditis in a dog, Journal of
Veterinary Cardiology (2016), http://dx.doi.org/10.1016/j.jvc.2016.03.001
5
myocarditis in the presence or absence of eosino-
philia and no identifiable cause.9 In a recent case
series examining seven human patients with eosi-
nophilic myocarditis, clinical signs varied between
low grade fever, dyspnea, systolic heart murmur,
and neurological abnormalities.10 All of the patients
had peripheral eosinophilia and all but one had
elevations of cardiac enzymes. On echocardiogram,
patients had left ventricular hypertrophy, left ven-
tricular focal asynergy, diffuse severe hypokinesis,
pericardial effusion, and/or thrombosis in the right
ventricle, left ventricle, or pulmonary artery.10 The
diagnosis of eosinophilic myocarditis was based on
the presence of eosinophilia, chest pain or dyspnea,
elevated cardiac enzymes, changes in ECG, or
changes on echocardiogram.10 The changes seen on
echocardiogram in the present case included left
and right ventricular hypertrophy and hypokinesis of
the left ventricle, which have been reported in the
human literature.10 In a study reviewing 42 con-
firmed cases of all forms of myocarditis, left ven-
tricular dysfunction was commonly observed in 69%
of cases and 23% of cases also involved the right
ventricle.11,12 The authors in that study concluded
that the echocardiographic findings in patients with
eosinophilic myocarditis can be variable and non-
specific.12 The study concluded that response to
therapy should be evaluated by serial, rather than
solitary echocardiograms.
The gold standard for the diagnosis of eosino-
philic myocarditis in people is endomyocardial
biopsies.9 This is a highly invasive procedure and
can lead to the death of the patient as shown in
the present case. Therefore, combinations of
preliminary diagnostic tests including echo-
cardiography and hematology are useful in
screening potential eosinophilic endomyocarditis
cases and validating the need for endomyocardial
biopsies. In people, if echocardiographic changes
in myocardial architecture and peripheral eosino-
philia are present alone without any other abnor-
malities on the initial diagnostics then the heart is
the likely source of the pathology and confirmatory
endomyocardial biopsy is warranted.9 The treat-
ment in people when a specific infectious cause is
not found is an immunosuppressive dose of corti-
costeroids. If the eosinophilic myocarditis was
caused by a parasitic infection, the infection was
treated first, and then the patient was placed on
steroids. Prognosis can be difficult to determine
and is dependent on the underlying condition;
however, with appropriate therapy, this condition
can be managed in people and therefore treat-
ment can be applied to veterinary patients as well.
This case report details a case of eosinophilic
myocarditis in a Munsterlander dog. Eosinophilic
6 T.P. Keeshen et al.

myocarditis is a rare disease characterized by References

eosinophilic inflammation within the myocardium 1. Lilliehöök I, Tvedten H. Investigation of hypereosinophilia
and subsequent alterations in myocardial structure and potential treatments. Vet Clin North Am Small Anim
and function. Primary eosinophilic myocarditis Pract 2003;33:1359e1378.
presents with a wide array of clinical and echo- 2. Aroch I, Perl S, Markovics A. Disseminated eosinophilic dis-
ease resembling idiopathic hypereosinophilic syndrome in a
cardiographic abnormalities including a peripheral dog. Vet Rec 2001;149:386e389.
eosinophilia (seen more commonly in people), 3. Dubey JP, Black SS, Verma SK, Calero-Bernal R, Morris E,
ventricular wall thickening, and abnormal indices Hanson MA, Cooley AJ. Sarcocystis neurona schizonts-
of systolic function. Endomyocardial biopsy is associated encephalitis, chorioretinitis, and myositis in a
required for a definitive diagnosis. two-month-old dog simulating toxoplasmosis, and presence
of mature sarcocystis in muscles. Vet Parasitol 2014;202:
194e200.
4. Vangeel L, Houf K, Geldhof P, Nollet H, Vercruysse J,
Conflict of interest statement Ducatelle R, Chiers K. Intramuscular inoculation of cattle
with Sarcocystis antigen results in focal eosinophilic myo-
sitis. Vet Parasitol 2012;183:224e230.
The authors do not have any conflicts of interest to 5. Thieman KM, Kirkby KA, Flynn-Lurie A, Grooters AM,
disclose. Bacon NJ. Diagnosis and treatment of truncal cutaneous
pythiosis in a dog. JAVMA 2011;239:1232e1235.
6. Harris BJ, Constantino-Casas F, Archer J, Herrtage ME.
Loeffler’s endocarditis and bicavity eosinophilic effusions in
Supplementary data a dog with visceral mast cell tumour and hypereosinophilia.
J Comp Pathol 2013;149:429e433.
7. Bonanad C, Monmeneu JV, Lopez-Lereu MP. Loeffler endo-
Supplementary data related to this article can carditis of the left ventricle: cardiac magnetic resonance
be found at http://dx.doi.org/10.1016/j.jvc. findings. Heart Lung Circ 2013;12:1056e1057.
2016.03.001. 8. Correia AS, Gonçalves A, Araújo V, Almeida e Silva J,
Pereira JM, Pereira PR, Pizarro M, Silva JC, Maciel MJ.
Churg-Strauss syndrome presenting with eosinophilic myo-
carditis: a diagnostic challenge. Port J Cardiol 2013;32:
Video table 707e711.
9. Rizkallah J, Desautels A, Malik A, Zieroth S, Jassal D,
Video 1 Right parasternal The loop demonstrates
Hussain F, Cordova F. Eosinophilic myocarditis: two case
four chamber marked ventricular
reports and review of the literature. BMC Res Notes 2013;6:
view wall thickening of 538.
mixed echogenicity 10. Kawano S, Kato J, Kawano N, Yoshimura Y, Masuyama H,
and diminished left Fukunaga T, Sato Y, Maruyama H, Mihara K, Ueda A,
ventricular wall motion. Toyoda K, Imamura T, Kitamura K. Clinical features and
Video 2 Right parasternal The loop similarly shows outcomes of eosinophilic myocarditis patients treated with
transverse plane the marked left prednisolone at a single institution over a 27-year period.
ventricular Intern Med 2011;50:975e981.
wall thickening and 11. Pinamonti B, Alberti E, Cigalotto A, Dreas L, Salvi A,
Silvestri F, Camerini F. Echocardiographic findings in myo-
diminished wall motion.
carditis. Am J Cardiol 1988;62:285e291.
Video 3 Left cranial view The loop demonstrates
12. Magnani JW, Dec GW. Myocarditis: current trends in diag-
of the right marked thickening of the nosis and treatment. Circulation 2006;113:876e890.
atrium atrial wall with similar
changes in echogenicity
as noted within the
ventricular myocardium.

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Please cite this article in press as: Keeshen TP, et al., A case of an unexplained eosinophilic myocarditis in a dog, Journal of
Veterinary Cardiology (2016), http://dx.doi.org/10.1016/j.jvc.2016.03.001