J Cardiol 2007 Aug; 50（2）: 127 – 133Survival After Acute Necrotizing
Eosinophilic Myocarditis Complicating a Massive Left Ventricular
Mural Thrombus : A Case Report
MakotoShin-ichiro
Kiyotaka
Hitoshi

KONTANI, MD
TAKASHIMA, MD
OKURA, MD
TAKEMORI, MD

Koji

MAENO, MD

Nobuyoshi

TANAKA, MD

Hirokazu

OHASHI, MD＊1

Sakon

NORIKI, MD＊2

Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
An 81-year-old man was referred to our hospital with exertional dyspnea following cold-like symptoms.
Electrocardiography revealed ST elevation and positive T wave in leads Ⅰ, Ⅱ, aⅤL, aⅤF, and Ⅴ2−Ⅴ6. The
diagnosis was acute myocarditis complicating heart failure. He was conservatively managed. On hospitalday 8, brain infarction developed and echocardiography disclosed massive mural thrombus in the left ventricle. Left ventriculotomy was performed on hospital day 21 and histological examination showed inflammatory cell infiltration mainly composed of eosinophils and monocytes, degeneration of myocytes withreplacement fibrosis, and fresh fibrin thrombus overlaying the endocardium. These findings were compatible with a diagnosis of acute necrotizing eosinophilic myocarditis（ANEM）. He recovered uneventfully
without specific therapy. This case suggests that a subtype of ANEM might be self-limiting.
──────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2007 Aug; 50（2）: 127−133

Key Words■ Myocarditis（acute necrotizing eosinophilic）■ Cardiac surgery（left ventriculotomy）■ Thrombosis（left ventricular mural thrombus）

INTRODUCTION
The association between eosinophilia and heartdisease is well known.1−4）Eosinophil-related cardiac injuries involve various parts of the heart suchas the endocardium, myocardium of both atria andventricles or heart valves, and can be classified
under the comprehensive term eosinophilic heartdisease . 5）In this continuum, acute necrotizing
eosinophilic myocarditis（ANEM）is characterized

by an acute and fulminant clinical course.6−11）We
describe a rare patient who survived ANEM complicating a massive mural thrombus in the left ventricle（LV）.
CASE REPORTAn 81-year-old Japanese man with hypertension
and hyperlipidemia developed fever, generalmalaise, polyarthralgia and exertional dyspnea inApril 15, 2005. Four days later he consulted a gen-──────────────────────────────────────────────
福井県済生会病院 内科 : 〒 918−8503 福井県福井市和田中町舟橋 7−1 ; ＊ 1 福井循環器病院 心臓血管外科，福井 ; ＊ 2 福井大学
医学部 腫瘍病理学，福井Department of Internal Medicine, Fukui-ken Saiseikai Hospital, Fukui ; ＊ 1Department of Cardiovascular Surgery, Fukui CardiovascularCenter, Fukui ; ＊ 2Department of Tumor Pathology, University of Fukui Faculty of Medical Science, Fukui
Address for correspondence : KONTANI M, MD, Department of Internal Medicine, Fukui-ken Saiseikai Hospital, Funabashi 7−1,
Wadanaka-cho, Fukui, Fukui 918−8503 ; E-mail : shp@fukui.saiseikai.or.jp
Manuscript received February 21, 2007 ; revised April 23, 2007 ; accepted May 7, 2007

127

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Kontani, Takashima, Okura et al

V1ⅠV2ⅡV3

ⅢaVR

V4aVL

V5aVFV6Fig. 1 Chest radiograph（left）and electrocardiogram（right）findings on admission
Chest radiography shows cardiomegaly, bilateral lung congestion and pleural effusion. Electrocardiogramshows sinus rhythm with ST elevation and positive T wave in Ⅰ, Ⅱ aⅤL, aⅤF, and Ⅴ2−Ⅴ6.

eral practitioner. Laboratory tests disclosed elevatedaminotransferase levels and he was referred to ourhospital. He had never developed allergic diasthesis, and had not received additional medication ora different prescription before the symptoms
appeared.
On admission, he was afebrile with blood pressure of 170/44 mmHg and a pulse of 78 beats/min.
Skin rash and edema were absent. Gallop rhythm,
heart murmur, crackles or rubs were inaudible. The
hepatojugular reflux was positive. Chest radiography showed cardiomegaly, bilateral lung congestionand pleural effusion（Fig. 1−left）. Electrocardiography revealed sinus rhythm with ST elevationand positive T wave in leads Ⅰ, Ⅱ, aⅤL, aⅤF, andⅤ2−Ⅴ（Fig.
1−right）.
6
Laboratory data demonstrated elevated whiteblood cell count without eosinophilia. Serum levelsof lactate dehydrogenase and creatine kinase wereelevated and the rapid assay for serum troponin T
was positive. Arterial blood gas analysis showedmetabolic acidosis accompanied by respiratorycompensation. Blood coagulation markers such as
fibrin degradation products and D-dimer were elevated（Table 1）. Autoantibodies such as antinuclear

Table 1 Laboratory data on admission
11,200/μl

BUN

Neutro81.0％

Cr

1.3 mg/dl

Lymph

12.5％

Na133 mEq/l

Eosino0.0％

K

4.5 mEq/l

Baso0.0％

Cl95 mEq/l

6.5％

Troponin TWBC

MonoRBC

475×104/μl
14.4 g/dl

HbHt

42.9％

Plt

16.6×104/μl

BloodProtein
Ketone（＋）

Myosin light chain 1 17.6 pg/ml
24.9 mg/dl
CRP
BNP

682.0 pg/ml

19.9 sec（PT-INR 1.74）
APTT 42.1 sec（control 32.9 sec）
PT

ESR 70/101 mm（1 hr/2 hr） Fbg
Urine

61.2mg/dl

FDP（2＋） D-dimer（2−） ATⅢ

535 mg/dl
392.2μg/ml
58.5μg/ml
60%（−）

AST

3,426 IU/l

ALT2,499 IU/l

Arterial blood gas（room air）
7.458
pHLDH404 IU/l

PO291.2 Torr

ALP

3,238 IU/l

PCO225.0 Torrγ-GTP

76 IU/lBE−4.7 mmol/l

CK340 IU/l

SO297.4%

CK-MB

31 IU/l

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Acute Necrotizing Eosinophilic Myocarditis

129Fig. 2 Serial changes in echocardiograms
A : Mural thrombus in left ventricle was present on admission（arrowheads）.
B : Massive mural thrombus was found in the apex of the left ventricle, partly floating in the left ventricularchamber（arrowheads）when cerebral infarction appeared on following day.
C : Left ventricular thrombus with reduced attachment to the lateral aspect of left ventricular endocardium
near the apex with thin stalks and mobility in the left ventricular chamber on day 20（24 hr before surgery）.
ED ＝ enddiastole ; ES ＝ endsystole.

antibody, anti-DNA and antineutrophilic antibodies
as well as levels of serum antibodies to viruses
were not elevated. Echocardiography demonstrated
diffuse hypokinesis of the LV, especially severe in. The LV
the anteroseptal to apical walls（Fig. 2−A）
wall was diffusely thickened and low echoic, suggestive of LV wall edema often seen in the acutephase of myocarditis.
An oral angiotensin converting enzyme inhibitorand spironolactone were administered based on adiagnosis of acute myocarditis, probably caused byviral infection with congestive heart failure, but
peripheral edema became evident. Intravenous
carperitide and dopamine were added, which ameliorated the lung congestion and peripheral edema.
Dysphagia, dysarthria and mild left hemiparesis
appeared on hospital day 8. Brain magnetic resonance imaging demonstrated fresh cerebral infarction in the right cerebral cortex（ Fig. 3）. Echocardiography revealed a massive mural thrombus in
the LV apex（Fig. 2−B）
, part of which was floating. Retroin the LV chamber（Fig. 2−B, arrowheads）
J Cardiol 2007 Aug; 50（2）: 127 – 133

spectively, the thrombus was already visible on theechocardiogram on admission（Fig. 2−A）. As thethrombus was thought to be the source of the cerebral embolism, unfractionated heparin was started
and then switched to warfarin.
By hospital day 20, the size of the LV thrombus
was reduced but it remained attached to the lateral
aspect of the LV endocardium with thin stalks thatwere mobile in the LV chamber as a whole（Fig. 2−C）
. Global LV contractility was improved and theLV wall echogenicity was increased. Doppler studies of mitral inflow velocity showed an abnormal
relaxation pattern with E/A ratio of 0.67 and diastolic descent rate（ DDR）of 221 msec. Retrospectively, the echocardiogram on admission hadrevealed restrictive pattern of LV diastolic dysfunction, so-called pseudonormalization（E/A ratio ＝1.24, DDR ＝ 165 msec）.
He was transferred to the cardiovascular surgery
department where left ventriculotomy was performed on the following day. Histological examination of the excised surgical specimen disclosed

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Kontani, Takashima, Okura et alA

BC

Fig. 3 Magnetic resonance images on hospital day 8
A : Diffusion-weighted image showed a high intensity area in the area of the middle cerebral artery of theright cerebral cortex（arrow）, which suggested fresh cerebral infarction.
B, C : T1-weighted image（B）and T2-weighted image（C）disclosed old cerebral infarctions（arrowheads）.

A1A2BC

Fig. 4 Photomicrographs of excised left ventricular myocardium（hematoxylin-eosin staining）
A1, A2 : Inflammatory cell infiltration mainly consisted of eosinophils and monocytes. Granulomas or multinucleated cells are absent（A1 : × 100, A2 : × 400）.
B : Degeneration and necrosis of myocytes（× 20）.
C : Granulation and fibrosis replacing degenerated myocytes（× 40）.

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Acute Necrotizing Eosinophilic Myocarditis

131ACB

Fig. 5 Photomicrographs of excised left ventricular thrombus（hematoxylin-eosin staining）
A : Layer of fresh fibrin thrombus with sparse monocyte infiltration diffusely overlays endocardium（× 20）.
B, C : Identical composition of mural thrombus and thin stalks anchoring thrombus, fibrin thrombus withsparse cellular infiltration（B, C : × 40）.
Abbreviation as in Fig. 4.

inflammatory cell infiltration mainly composed ofeosinophils and monocytes（ Figs. 4−A1, A2）.
Degeneration and necrosis of myocytes（Fig. 4−B）
was replaced by granulation and fibrosis（Fig. 4−C）. Granulomas and multinucleated cells wereabsent. These findings were compatible with thefeatures of ANEM. A layer of fresh fibrin thrombus
with sparse monocyte infiltration diffusely overlaid
the endocardium（Fig. 5−A）, which is also a frequent feature of eosinophilic heart disease.12, 13）The
composition of the floating mass and stalks was thesame（Figs. 5−B, C）.
The blood eosinophil count peaked at 740/mm3
on hospital day 27. The patient made an uneventful
recovery and has remained well without immunosuppressive agents.
DISCUSSION
Within the spectrum of eosinophilic heart diseases, ANEM is the most lethal, and has such a fulminant clinical course that the diagnosis is often
J Cardiol 2007 Aug; 50（2）: 127 – 133

only established at autopsy or necropsy. 6,7,9）
However, high dose corticosteroid after histologicaldiagnosis with endomyocardial biopsy has had
some success.8,10）Only four cases of survival from
ANEM have been reported.8,10,11,14）In addition, thepresent patient had some intriguing features compared with other reports.
Firstly, he survived without specific therapy suchas corticosteroid administration. A patient withANEM rapidly recovered after pericardial drainage
without corticosteroid therapy.11）Elevated interleukin（IL）-5 concentration was found in the pericardial effusion during the acute phase of ANEM,
suggesting that the reduction of IL-5 and of othercytokines such as IL-13 15）in the heart induced bypericardial drainage might have reduced tissue
eosinophil activities resulting in a benign clinicalcourse. The pericardium of our patient was also
opened and irrigated during surgery. However, incontrast to the previous patient, pericardiotomy wasperformed during the convalescent phase.

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Kontani, Takashima, Okura et al

Therefore, the benign clinical course of our patientwas not a likely consequence of the pericardiotomy
and implies that a self-limiting subtype of ANEM
may occur in patients with histologically undiagnosed acute myocarditis.
Secondly, blood eosinophilia did not appear during the entire clinical course. Other reports ofpatients who have survived ANEM often describedabsent or mild blood eosinophilia.8,10）This suggeststhat a low blood eosinophil count indicates a good
prognosis for patients with ANEM. On the other
hand, the absence of blood eosinophilia makes it
difficult to differentiate ANEM from lymphocytic
myocarditis based only on the clinical presentationand noninvasive laboratory data. Therefore, earlysuspicion of ANEM and performance of endomyocardial biopsy, and early institution of corticosteroid therapy according to the histological diagnosis might be crucial for patient survival.
Thirdly, a massive LV mural thrombus led tocerebral thromboembolism in our patient, which isapparently unique in a living patient with ANEM.
Eosinophilic heart disease is associated withendomyocardial inflammation and subsequentmural thrombi.1,3−5,12,13）The histology of patientswith Loeffler s endocarditis indicates that a stage of
myocardial necrosis arises during the acute phase
要of the disease and leads to a thrombotic stage inwhich eosinophils cause endocardial damage andresultant ventricular mural thrombi.12）Histologicalstudy has showed that eosinophils adhere to theendocardium with various degrees of endocardial
thickening accompanied by diffuse myocyte necrosis, 11）which seems comparable with this acutenecrotic stage.12）Therefore, the pathophysiologicallikelihood of mural thrombi arising in ANEM ishigh. Conversely, the probability of eosinophilic
heart disease should be determined by endomyocardial biopsy if intracardiac thrombi appear during
the active phase of acute myocarditis.
The present patient had ANEM with unusual
symptoms, suggesting that a benign self-limiting
subtype of ANEM could be associated with absent
or mild blood eosinophilia. We recommend thatearly histological diagnosis with prompt endomyocardial biopsy should be considered for patientswith acute myocarditis irrespective of the degree ofeosinophilia, especially if hemodynamic deterioration is rapid and/or mural thrombus is a complicating factor. This procedure would differentiate
ANEM from other types of myocarditis and impact
decisions about the application of corticosteroid
therapy.

約左室壁在血栓を合併した急性壊死性好酸球性心筋炎の 1 生存例
紺 谷真

前野孝治

高島伸一郎

大倉清孝

竹森一司

田中

大橋博和

法木左近延善症例は 81 歳，男性．2005 年 8 月，発熱・多関節筋肉痛に引き続き労作時息切れが出現した．4 日
後，近医にてアミノトランスフェラーゼ上昇を指摘され，翌日当院に紹介入院した．心電図上Ⅰ，Ⅱ，aⅤL，aⅤF およびⅤ2−Ⅴ6 誘導に ST 上昇と陽性 T 波を認めた．両心不全を合併した急性心筋炎と診断，保存的治療を開始した．第 8 病日に脳梗塞を発症，心エコー図検査により左室に壁在血栓を認めた．抗凝固療法を行うも血栓塞栓再発の可能性が高いと判断し第 21 病日に左室切除術を施行した．病理組織検査により主に好酸球と単核球からなる炎症細胞浸潤，置換性繊維化を伴う心筋細胞変性，心内膜全体を覆うフィブリン血栓を認めた．以上の所見から組織学的に急性壊死性好酸球性心筋炎と診断した．以後，特殊治療なしに自然軽快した．急性壊死性好酸球性心筋炎は急激な血行動態悪化を示し予後不良とされるが，予後良好な亜型が存在する可能性がある．

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Acute Necrotizing Eosinophilic Myocarditis

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