ESC HEART FAILURE
CASE REPORTESC Heart Failure 2020; 7: 4315–4319
Published online 11 September 2020 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ehf2.12984

Cardiac involvement with anti‐mitochondrial antibody‐
positive myositis mimicking cardiac sarcoidosis
Takahide Kadosaka1, Shingo Tsujinaga1*, Hiroyuki Iwano1, Kiwamu Kamiya1, Azusa Nagai2, Yoshifumi
Mizuguchi1, Ko Motoi1, Kazunori Omote1, Toshiyuki Nagai1, Ichiro Yabe2 and Toshihisa Anzai1
1
Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; 2Department of Neurology, Faculty ofMedicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

Abstract
Anti‐mitochondrial antibody (AMA)‐positive myositis is an atypical inﬂammatory myopathy characterized by chronic progressive respiratory muscle weakness, muscular atrophy, and cardiac involvement. Arrhythmias, cardiomyopathy, and myocarditis
have been reported as cardiac manifestations. Herein, we present the ﬁrst report of a patient diagnosed with having
AMA‐positive myositis with cardiac involvement mimicking cardiac sarcoidosis.
Keywords

Anti‐mitochondrial antibody; Anti‐mitochondrial antibody‐positive myositis; Cardiac sarcoidosis

Received: 19 May 2020; Revised: 9 August 2020; Accepted: 13 August 2020
*Correspondence to: Shingo Tsujinaga, Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7,Kita-ku, Sapporo 060-8638, Japan. Tel: +81-11-706-5755; Fax: +81-11-706-6973.
Email: shingo-t.0207@med.hokudai.ac.jp

Introduction
Inﬂammatory myopathy occurring in association withanti‐mitochondrial antibody (AMA) is rare, but there is a
growing recognition for this clinical entity. AMA‐positive myositis is an atypical inﬂammatory myopathy that is characterized by chronic progressive respiratory muscle weakness,muscular atrophy, and cardiac involvement.1 Cardiac lesions
include arrhythmias, cardiomyopathy, and myocarditis.2
Although varied cardiac manifestations such as regional wallmotion abnormality in the left ventricle (LV) without
dilation,3 dilated cardiomyopathy (DCM)‐like LV systolic
dysfunction,4 and arrhythmogenic right ventricular cardiomyopathy (ARVC)‐like right ventricular dysfunction have beenreported,5 no typical cardiac ﬁndings have been described.
Herein, we report the case of a middle‐aged man who wasdiagnosed as having AMA‐positive myositis associated withcardiac involvement mimicking cardiac sarcoidosis.

Case report
A 55‐year‐old man sought medical attention because of progressive difﬁculty in getting up from sitting and difﬁculty inbreathing for 2 months. He had a history of weakness in
the lower limbs and fatigue for 9 years. He had been evaluated in another centre for the present complaints where anechocardiogram had revealed LV systolic dysfunction. Hewas then referred to our department and admitted for themanagement of his worsening symptoms.
The physical examination at admission revealed that hewas 158 cm tall and weighed 39 kg. His body mass index(BMI) was 15.6 kg/m2. His breathing was shallow, and he
was tachypnoeic. His pulse rate was 64/min, blood pressure
was 106/74 mmHg, and transcutaneous oxygen saturation
was 98% in room air. Clinical examination revealed no distension of the jugular vein, heart murmur, third heart sound, orpedal oedema. His power on neurological examination of thelimb muscles revealed mild weakness in the proximal muscles(manual muscle test score 4), and Gowers’ sign was positive.
Chest radiography showed no cardiomegaly or lung congestion (Figure 1A). Electrocardiogram showed poor R wave
progression and ST segment elevation in the right precordial
leads (V1–4) (Figure 1B). The laboratory tests revealed anincreased level of serum N‐terminal‐pro‐B‐type natriuretic
peptide (1900 pg/mL) and troponin T (36 ng/L). The serum
level of creatine kinase was normal (175 IU/L). The
angiotensin‐converting enzyme level was below the normal© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium,provided the original work is properly cited, the use is non‐commercial and no modiﬁcations or adaptations are made.

4316

T. Kadosaka et al.

Figure 1 (A) The chest radiograph at admission showing no cardiomegaly or lung congestion. (B) The electrocardiogram at admission showing poor R
wave progression and ST segment elevation in the right precordial leads (V1–4).

value (0.6 U/L); and liver function test results including thosefor bilirubin, transaminases, alkaline phosphatase, andgamma‐glutamyl transpeptidase were normal. The computed
tomography of the liver revealed no liver abnormal morphology. Echocardiography showed LV wall thinning in the basal
anteroseptum and middle level of inferoseptum walls (Figure2A, Video S1) and extensive LV asynergies in the interventricular septum and inferior and posterior walls accompanied byan aneurysm from the middle level of the inferoseptal to posterior walls (Figure 2B, Video S2) with decreased LV ejection
fraction (EF) (LVEF) (41%). These echocardiographic ﬁndings
were interpreted as highly suggestive of cardiac sarcoidosis.
Cardiac magnetic resonance imaging (CMRI) also revealed
delayed gadolinium enhancement in the middle layers of
the LV portion of the interventricular septum and inferiorand posterior walls (Figure 3), which was consistent withthe ﬁndings of cardiac sarcoidosis. However, subsequent
18
F‐ﬂuorodeoxyglucose (FDG) positron emission tomography(PET) revealed no abnormal FDG uptake in the LV

myocardium (Figure 4). The patient had no previous historyof advanced atrioventricular block or fatal ventriculararrhythmia. A coronary angiogram showed no stenotic
lesions, and the histopathological ﬁndings in an
endomyocardial biopsy (EMB) specimen obtained from theright side of the interventricular septum showed no evidenceof cardiac sarcoidosis, myocardial ﬁbrosis, or secondary cardiomyopathy (Figure 5A, B). Screening of other organs including the lung, eye, and skin showed no evidence of systemic
sarcoidosis. Hence, myositis was considered as a possibility
because of proximal limb muscle weakness with an impaired
6 min walk test (120 m) and a severe restrictive pattern on
pulmonary function tests [vital capacity 1.08 L (30% ofpredicted values)]. Thus, a neurological consult was obtained.
Autoimmune antibodies were measured and positive foranti‐nuclear antibodies (≧1:640), AMA (118.0 index), andrheumatoid factor (27.1 IU/L); and other autoantibodies werenegative. Electromyogram examination showed low amplitude in quadriceps muscle and biceps brachii muscle. Nerve

Figure 2 (A) Parasternal long‐axis echocardiographic view at end‐diastole showing left ventricular wall thinning in the basal anteroseptal (yellow arrow) and mid‐inferoseptal (yellow dotted arrow) walls. (B) Apical two‐chamber echocardiographic view showing an aneurysm from the
mid‐inferoseptum to the posterior walls (red arrow).

ESC Heart Failure 2020; 7: 4315–4319
DOI: 10.1002/ehf2.129844317

Cardiac involvement with AMA‐positive myositis

Figure 3 (A) Cardiac magnetic resonance (CMR) in the short‐axis view showing delayed gadolinium enhancement in the middle layers of left ventricular (LV) anteroseptal, inferoseptal, posterior, and lateral walls (yellow arrows). (B) CMR in the long‐axis view showing delayed gadolinium enhancement in the middle layers of LV anteroseptal, inferoseptal, and posterior walls (yellow arrows).

Figure 418

F‐Fluorodeoxyglucose (FDG) positron emission tomography (PET) showing no abnormal FDG uptake in the left ventricular (LV) myocardium.

conduction study showed no abnormalities. Muscle biopsy of
the left biceps brachii demonstrated sporadic necrotic ﬁbres(Figure 6A, B) but no ﬁndings of mitochondrial myopathy,
dystrophinopathy, and dysferlinopathy.
The patient was, therefore, diagnosed as having
AMA‐positive myositis; and the LV dysfunction was thought
to be caused by cardiac involvement associated with themyositis. Non‐invasive positive pressure ventilation (NPPV)
using bilevel positive airway pressure was initiated forrespiratory support. After one course of intravenous methylprednisolone, pulse therapy (1 g/day for 3 days) wasadministered, and high‐dose oral prednisolone therapy(50 mg/day) was started. The dose was subsequently reducedby 10 mg each week to 5 mg/day. Oral cardioprotective
drugs, such as enalapril (2.5 mg/day) and bisoprolol(2.5 mg/day), were also administered. Once muscularsymptoms and dyspnoea were relieved, NPPV wasdiscontinued. One month after treatment, the 6 min walktest (250 m) and pulmonary function tests [vital capacity
1.50 L (43% of predicted values)] had improved. Follow‐up
echocardiogram showed mild recovery in LV systolic function(LVEF: 43%), even though it had not returned to normal.
Currently, we are carefully observing the clinical course of
the disease in the patient for 3 months.

Discussion
AMA is most commonly found in association with primary biliary cirrhosis6; however, it has also been linked to idiopathic
inﬂammatory myopathies.1 The frequency of AMA‐positive
ESC Heart Failure 2020; 7: 4315–4319
DOI: 10.1002/ehf2.12984

4318

T. Kadosaka et al.

Figure 5 (A) Histopathological ﬁndings showed no evidence of cardiac sarcoidosis, myocardial ﬁbrosis, or ﬁndings speciﬁc for secondary cardiomyopathy (haematoxylin–eosin stain, ×400, dimensional bar = 100 μm). (B) Electron microscopy showed no ﬁndings suggestive of cardiac sarcoidosis orother secondary cardiomyopathy.

Figure 6 Muscle biopsy of the left biceps brachii showing ﬁbre size variation, sporadic necrotic ﬁbres, and few inﬂammatory cell inﬁltration (A,haematoxylin–eosin stain; B, modiﬁed Gomori Trichrome Stain, dimensional bar = 100 μm).

myositis in idiopathic inﬂammatory myopathies is reported tovary depending on the country: Japan (11.3–19.5%), France(7.8%), China (5.15%), and North America (0.6%).1,2,5,6
AMA‐positive myositis is characterized by chronic progressive
respiratory muscle weakness, muscular atrophy, and cardiac
involvement.1 Among these patients, 20–30% have cardiac
involvement including arrhythmias and LV dysfunction.1,7Cardiac involvement including a local wall motion abnormality in the LV without dilation and decreased LVEF or
DCM‐like or ARVC‐like ﬁndings is reported3–5; however,characteristic features have not been elucidated.
In this particular patient, initially, cardiac sarcoidosis wasstrongly suspected from echocardiographic and CMR ﬁndings
including LV wall thinning in the basal anteroseptal or mid
inferoseptal walls, extensive LV asynergy accompanied byan aneurysm, and delayed gadolinium enhancement in themiddle layers of the LV walls. These were consistent withthe typical ﬁndings of cardiac sarcoidosis.8 However, in thispatient, FDG‐PET revealed no abnormal FDG uptake in theLV myocardium, EMB showed no evidence of cardiac sarcoidosis, and other organs showed no evidence of systemic
sarcoidosis. The patient did not match any expert consensus
recommendations on the criteria for the diagnosis of cardiac
sarcoidosis.8 Based on suspected myositis‐related symptoms
such as very low BMI, muscle weakness and a severe
restrictive pattern on pulmonary function, myositis was considered. Finally, he was diagnosed as having AMA‐positivemyositis on the basis of his neurological symptoms.
In summary, the cause of LV systolic dysfunction in thiscase was considered to be cardiac involvement associatedwith AMA‐positive myositis. Intriguingly, the cardiac morphology in this case mimicked cardiac sarcoidosis. However,ESC Heart Failure 2020; 7: 4315–4319
DOI: 10.1002/ehf2.12984

4319

Cardiac involvement with AMA‐positive myositis

the inﬂuence of immunosuppressive therapy on cardiac
involvement with AMA‐positive myositis is unknown.1–3 In
this patient, improvements in muscle symptoms wereobserved, but no signiﬁcant improvement in cardiac involvement was observed at 1 month after treatment, which
necessitates careful follow‐up of cardiac function.
To the best of our knowledge, this is the ﬁrst report of cardiac involvement in a patient with AMA‐positive myositis
mimicking cardiac sarcoidosis. This was an educational casesuggesting that AMA‐positive myositis with cardiac involvement should be considered as a differential diagnosis whenmuscle symptoms such as respiratory muscle weakness andmuscular atrophy are present, even if the cardiac morphology
is suggestive of cardiac sarcoidosis.

Conﬂict of interest

FundingNone.

Supporting information
Additional supporting information may be found online in the
Supporting Information section at the end of the article.
Video S1. Transthoracic echocardiography in parasternal
long‐axis view demonstrates left ventricular wall thinning in
the basal anteroseptum and middle level of inferoseptum
walls.
Video S2. Transthoracic echocardiography in apicaltwo‐chamber view demonstrates an aneurysm from themid‐inferoseptum to the posterior walls.

None declared.

References
1. Maeda MH, Tsuji S, Shimizu J. Inﬂammatorymyopathies
associatedwithanti‐mitochondrial antibodies. Brain
2012; 135: 1767–1777.
2. Albayda J, Khan A, Casciola‐Rosen L,Corse AM, Paik JJ, Christopher‐Stine L.
Inﬂammatory myopathy associated withanti‐mitochondrial antibodies: a distinct
phenotype with cardiac involvement.
Semin Arthritis Rheum 2018; 47:
552–556.
3. Bujo S, Amiya E, Kojima T, Yamada S,Maki H, Ishizuka M, Uehara M, Hosoya Y,Hatano M, Kubota A, Toda T, Komuro I.
Variable cardiac responses to immunosuppressive therapy in anti‐mitochondrialantibody‐positive myositis. Can J Cardiol.
2019 Nov; 35: 1604 e1609–1604 e1612.
4. Tanaka K, Sato A, Kasuga K, Kanazawa M,Yanagawa K, Umeda M, Tada M, Tanaka
M, Nishizawa M. Chronic myositis withcardiomyopathy and respiratory failure
associated
with
mild
form
oforgan‐speciﬁc autoimmune diseases. Clin
Rheumatol 2007; 26: 1917–1919.
5. Uenaka T, Kowa H, Ohtsuka Y, Seki T,
Sekiguchi K, Kanda F, Toda T. Less limb
muscle involvement in myositis patientswith anti‐mitochondrial antibodies. EurNeurol 2017; 78: 290–295.
6. Hou Y, Liu M, Luo YB, Sun Y, Shao K, Dai
T, Li W, Zhao Y, Yan C. Idiopathic

inﬂammatory
myopathies
withanti‐mitochondrial antibodies: clinicalfeatures and treatment outcomes in a Chinese cohort. Neuromuscul Disord 2019;29: 5–13.
7. Koyama M, Yano T, Kikuchi K, Nagahara
D, Ishibashi‐Ueda H, Miura T. Lethal
heart failure with anti‐mitochondrial antibody: an arrhythmogenic right ventricularcardiomyopathy mimetic. Eur Heart J
2017; 38: 123.
8. Birnie DH, Kandolin R, Nery PB, Kupari
M. Cardiac manifestations of sarcoidosis:diagnosis and management. Eur Heart J
2017; 38: 2663–2670.

ESC Heart Failure 2020; 7: 4315–4319
DOI: 10.1002/ehf2.12984