International Journal of Clinical Medicine, 2011, 2, 260-263
doi:10.4236/ijcm.2011.23041 Published Online July 2011 (http://www.SciRP.org/journal/ijcm)
Clinical Feature of Japanese Patients with
Fulminant Myocarditis
—Myocarditis in Japanese Patients
Hiroaki Kawano1*, Yasuhiro Nagayoshi2, Sunao Kojima2, Nahoko Kakihara3, Satoshi Sakuma1,
Masumi Uchino1, Aiko Komatsu1, Machiko Asaka1, Mitsuhiro Shimomura1, Hiroshige Yamabe2,
Hisao Ogawa2, Koichi Node1
1Department of Cardiovascular Medicine, Saga University, Saga, Japan; 2Department of Cardiovascular Medicine, Graduate School
of Medical Sciences, Kumamoto University, Kumamoto, Japan; 3Department of Basic Science of Nursing, Division of Function and
Morphology for Nursing, Saga University, Saga, Japan.
Received April 20th, 2011; revised May 27th, 2011; accepted June 7th, 2011.
ABSTRACT
Fulminant myocarditis is commonly recognized as an acute myocarditis with cardiogenic shock requiring mechanical
support systems. Before the development of mechanical assist devices, previous study described that most of patients
with fulminant myocarditis die at acute phase because of rapidly progressive cardiac decompensation. To investigate
the feature of myocarditis, we checked consecutive 18 patients (10 men, 8 women, (12 yr - 80 yr)) from April in 2001 to
September 2008 in University. Of these patients 3 needed intra-aortic balloon pumping (IABP) (2 men, 1 woman), 6 did
both IABP and percutaneous card iopulmonary support (PCPS) (2 men, 4 women). Three patients who need both IABP
and PCPS died (2 men, 49 yr and 65 yr, 1 woman, 54 yr) because of uncontrolled bacterial infection . No patients whose
age was under 40 yr (5 men, 4 women) died although a man needed IABP and 3 women did both IABP and PCPS. Six-
teen patients were able to resume a normal life although 1 male patient needed permanent pacemaker, 1 female did
cardiac resynch ronizatio n therapy, and a male and a fema le had left ventricular systo lic dysfunction. In conclu sion, the
young patients had better prognosis than older even if mechanical assist is needed. Although half of patients needed
mechanical assist, the prevention of multi-organ complications including bacterial infection is one of the most impor-
tant keys in the treatment of fulminant myocarditis.
Keywords: Myocarditis, Mechanical Support, Immunosuppressive Therapy, Immunomodulation Therapy
1. Introduction
Myocarditis is one of the most challenging diagnoses for
cardiologists. The entity is rarely recognized, the patho-
physiology is poorly understood, there is no commonly
accepted diagnostic gold standard and all current treat-
ment is controversial. The prevalence of myocarditis has
been found to be up to 42% in case of unexplained death
in people aged 35 or younger [1,2].
Acute myocarditis, especially fulminant myocarditis,
still causes substantial morbidity and mortality, espe-
cially in children and young adults. Fulminant myocardi-
tis is commonly recognized as an acute myocarditis with
cardiogenic shock requiring artificial mechanical support
systems [3,4]. Recently, because of the use of steroids
and immunoglobulin as well as mechanical circulatory
assist devices, such as intra-aortic balloon pumping
(IABP), percutaneous cardiopulmonary support (PCPS),
and left ventricular assist devices, the acute stage sur-
vival of fulminant myocarditis have been improved [5-8].
Mechanical circulatory support has become the standard
therapy to bridge patients with intractable heart failure to
either transplantation or myocardial recovery.
In the present study, we report the feature of Japanese
patients with fulminant myocarditis who hospitalized be-
tween 2001 and 2008 in our institute.
2. Methods
Before the development of mechanical assist devices,
previous study described that a lot of patients with ful-
minant myocarditis die at acute phase because of rapidly
progressive cardiac decompensation [10]. From April in
2001 to September 2008, we had 18 patients with fulmi-

Clinical Feature of Japanese Patients with Fulminant Myocarditis261
nant myocarditis who had severe heart failure (New York
Heart Association IV) in our institute. All had cardiac
symptoms and clinical suspicion of myocarditis in the
absence of known non-inflammatory causes including
coronary artery disease. We did transthoracic Doppler
echocardiography, complete heart catheterization and
selective coronary angiography in all patients. Ejection
fraction (EF) was measured by Simpson methods with
echocardiography.
Endomyocardial biopsy is the critical test to confirm
the diagnosis. Unfortunately, we were not able to per-
form endomyocardial biopsy in all patients because of
the unstable circulation due to myocarditis. Thus, myo-
carditis had been diagnosed with clinical symptoms,
physical examinations, heart catheterization, electrocar-
diogram and echocardiography [9]. All subjects gave
written, informed consent, and the study was approved
by the ethics committee at our institution.
3. Results
The etiology of myocarditis had been suspected viral
infection. Of 18 patients, 3 needed intra-aortic balloon
pumping (IABP) (2 men, 1 woman), 6 did both IABP
and percutaneous cardiopulmonary support (PCPS) (2
men, 4 women) as shown in Table 1. Three patients who
need both IABP and PCPS died (2 men, 49 yr and 65 yr,
1 woman, 54 yr) because of uncontrolled bacterial infec-
tion. No patients whose age was under 40 yr (5 men, 4
women) died although a man needed IABP and 3 women
did both IABP and PCPS. Sixteen patients were able to
resume a normal life although 1 male patient needed
permanent pacemaker, 1 female did cardiac resynchroni-
zation therapy, and a male and a female had left ven-
tricular systolic dysfunction.
4. Discussion
Multiple infectious etiologies had been implicated as the
cause of myocarditis, the most common being viral [11].
In the majority of patients, active myocarditis remains
unsuspected because the cardiac dysfunction is subclini-
cal and self-limited. In the present study, the etiology of
myocarditis had not been able to defined, but been sus-
pected viral infection in all study patients.
The cornerstone of therapy for patients with acute
myocarditis is supportive care [11]. Serial echocardi-
ography, right heart catheterization, etc., are all em-
ployed determine native cardiac reserve and suitability
for device choose. We present the feature of 18 patients
with fulminant myocarditis including a 20-year old
woman with long term non-responsive cardiac arrest re-
turning to normal life. In many cases with fulminant
myocarditis, it is difficult to maintain good circulatory
function with mechanical support devices, including ven-
tilation, pacing, IABP, PCPS, etc., because of several
critical complications. Thus, it is important to maintain
good circulatory support to allow sufficient time for
resolution of cardiac inflammation and improvement in
ventricular function. We had to pay much attention to
prevent multi-organ complications and circulatory insuf-
ficiency, and to control bacterial infection control during
Table 1. Patients characteristics.
No. Age (yr) Mechanical support Immunosuppressive & Immunomodulation therapy EF(%)
man
1 18 23
2 22 22
3 24 Corticosteroid 23
4 34 IABP (for 4 days) Corticosteroid + IVIG 12
5 38 IABP (for 9 days) Corticosteroid + IVIG 11
6 49 PCPS + IABP (for 11 days) 12 (dead)
7 59 23
8 65 PCPS (for 8 days) 20 (dead)
9 68 Pacing (for 3 days) 31
10 80 Pacing → permanent pacemaker 23
woman
1 12 PCPS + IABP (for 5 days) Corticosteroid + IVIG (see Figure 1) 24
2 16 PCPS + IABP + Pacing (for 7 days) Corticosteroid + IVIG 12
3 20 PCPS + IABP + Pacing (for 9 days)
→ cardiac resynchronization therapy
Corticosteroid + IVIG 13
4 30 20
5 49 21
6 54 PCPS + IABP (for 9 days) Corticosteroid + IVIG 13 (dead)
7 56 14 (dead)
8 71 IABP (for 7 days) Corticosteroid + IVIG 19
EFejection fraction; IABP: intra-aortic balloon pumping; IVIG: High-dose intravenous immune globulin; PCPS: percutaneous cardiopulmonary support. :

Clinical Feature of Japanese Patients with Fulminant Myocarditis
262
the mechanical support in order to resume a normal life.
Thus, several specialists, such as cardiologists, anesthe-
siologists, respiratory doctors, infection control teams,
mechanical support technicians, and skilful nurses, were
essential to care patients with fulminant myocarditis in
intensive care unit.
The treatment of myocarditis is controversial, and no
specific therapeutic regimen has been established [11].
All patients with myocarditis should receive standard
heart failure therapy. Immunosuppressive therapy has
been proposed to treat myocarditis in both children and
adults. The results of an international trail, the Myocardi-
tis Treatment Trial in 1995, showed that there was no
difference in heart function in the treated with immuno-
suppressive agents or placebo [12]. Despite the negative
results of this trail, the authors indicated that patients
who responded to immunosuppressive therapy appeared
to have higher initial ejection fraction and shorter dura-
tion of illness. High-dose intravenous immune globulin
(IVIG) has both immune modulatory and antiviral effects
[13-15]. However, there was no difference between pla-
cebo and IVIG. Thus, there was no benefit of immuno-
modulation. In the present study, some patients had im-
munosuppressive therapy, some had IVIG and some had
both. The present small study cannot conclude the effects
of the immunosuppressive and the immunomodulation
therapy for fulminant myocarditis. Taken as a whole, the
present small study together with previous trials, do not
support the routine use of immunosuppressive and im-
munomodulation therapy for fulminant myocarditis [16].
These data suggest that subgroup with ongoing fulminant
myocarditis, especially in the patients who need me-
chanical cardiac support, can be more likely to benefit
from immunosuppressive and immunomodulation ther-
apy, although no uniform methodology yet exists to
identify them.
Figure 1. Endomyocardial tissue of 12 yr woman with myo-
carditis (case 1). (Hematoxylin and Eosin stain).
In conclusion, the young patients had better prognosis
than older even if mechanical assist is needed. Although
half of patients needed mechanical assist, the prevention
of multi-organ complications including bacterial infec-
tion is one of the most important keys in the treatment of
fulminant myocarditis.
REFERENCES
[1] A. Doolan, N. Langlois and C. Semsarian, “Causes of
Sudden Cardiac Death in Young Australians,” The Medi-
cal Journal of Australia, Vol. 180, No. 3, 2004, pp.
110-112.
[2] B. J. Maron, “Sudden Death in Young Athletes,” The
New England Journal of Medicine, Vol. 349, 2003, pp.
1064-1075. doi:10.1056/NEJMra022783
[3] K. Kawahito, S. Murata, T. Yasu, H. Adachi, T. Ino, M.
Saito, et al., “Usefulness of Extracorporeal Membrane
Oxygenation for Treatment of Fulminant Myocarditis and
Circulatory Collapse,” The American Journal of Cardi-
ology, Vol. 82, No. 7, 1998, pp. 910-911.
doi:10.1016/S0002-9149(98)00503-7
[4] S. Kato, S. Morimoto, S. Hiramitsu, M. Nomura, T. Ito
and H. Hishida, “Use of Percutaneous Cardiopulmonary
Support of Patients with Fulminant Myocarditis and Car-
diogenic Shock for Improving Prognosis,” The American
Journal of Cardiology, Vol. 83, No. 7, 1999, pp. 623-625.
doi:10.1016/S0002-9149(98)00931-X
[5] Y. Inoue, H. Kaneko, Y. Yoshizawa and A. Morikawa,
“Rescue of a Child with Fulminant Myocarditis Using
Percutaneous Cardiopulmonary Support,” Pediatric Car-
diology, Vol. 21, No. 2, 2000, pp. 158-160.
doi:10.1007/s002469910026
[6] K. Kohno, N. Aoyama, T. Shimohama, M. Yoshida, Y.
Machida, N. Fukuda, et al., “Resuscitation from Fulmi-
nant Myocarditis Associated with Refractory Ventricular
Fibrillation,” Japanese Circulation Journal, Vol. 64, No.
2, 2000, pp. 139-143. doi:10.1253/jcj.64.139
[7] M. Arima, T. Kanoh, Y. Kawano, S. Okazaki, T. Oigawa,
S. Yamagami, et al., “Recurrence of Myocarditis Pre-
senting as Pacing and Sensing Failure after Implantation
of a Permanent Pacemaker at First Onset,” Japanese Cir-
culation Journal, Vol. 65, No. 4, 2001, pp. 345-348.
doi:10.1253/jcj.65.345
[8] A. Izawa, O. Kinoshita, Y. Shiba, W. Takahashi, S.
Uchikawa, H. Imamura, et al., “Percutaneous Cardiopul-
monary Support Aids Resuscitation from Sustained Ven-
tricular Tachycardia,” Circulation Journal, Vol. 67, No.
12, 2003, pp. 1061-1063. doi:10.1253/circj.67.1061
[9] G. M. Felker, “Echocardiographic Findings in Fulminant
and Acute Myocarditis,” Journal of the American College
of Cardiology, Vol. 36, No. 1, 2000, pp. 227-232.
doi:10.1016/S0735-1097(00)00690-2
[10] E. B. Lieberman, G. M. Hutchins, A. Herskowitz, N. R.
Rose and K. L. Baughman, “Clinicopathologic Descrip-
tion of Myocarditis,” Journal of the American College of
Cardiology, Vol. 18, No. 7, 1991, pp. 1617-1626.

Clinical Feature of Japanese Patients with Fulminant Myocarditis263
doi:10.1016/0735-1097(91)90493-S
[11] J. W. Magnani and G. W. Dec, “Myocarditis: Current
Trends in Diagnosis and Treatment,” Circulation, Vol.
113, 2006, pp. 876-890.
doi:10.1161/CIRCULATIONAHA.105.584532
[12] J. W. Mason, J. B. O'Connell, A. Herskowitz, N. R. Rose,
B. M. McManus, M. E. Billingham and T. E. Moon, “The
Myocarditis Treatment Trial Investigators, A Clinical
Trial of Immunosuppressive Therapy for Myocarditis,”
The New England Journal of Medicine, Vol. 333, 1995,
pp. 269-275. doi:10.1056/NEJM199508033330501
[13] D. M. McNamara, W. D. Rosenblum, K. M. Janosko, M.
K. Trost, F. S. Villaneuva, A. J. Demetris, S. Murali and
A. M. Feldman, “Intravenous Immune Globulin in the
Therapy of Myocarditis and Acute Cardiomyopathy,”
Circulation, Vol. 95, No. 11, 1997, pp. 2476-2478.
[14] D. M. McNamara, R. Holubkov, R. C. Starling, G. W.
Dec, E. Loh, G. GuillTorre-Amione, A. Gass, K. Janosko,
T. Tokarczyk, P. Kessler, D. L. Mann and A. M. Feldman,
“Controlled Trial of Intravenous Immune Globulin in
Recent-Onset Dilated Cardiomyopathy,” Circulation, Vol.
103, No. 18, 2001, pp. 2254-2259.
[15] K. Shioji, Y. Matsuura, T. Iwase, S. Kitaguchi, H. Naka-
mura, J. Yodoi, et al., “Successful Immunoglobulin
Treatment for Fulminant Myocarditis and Serial Analysis
of Serum Thioredoxin: A Case Report,” Circulation
Journal, Vol. 66, No. 10, 2002, pp. 977-980.
doi:10.1253/circj.66.977
[16] L. T. Cooper Jr., “Myocarditis,” The New England
Journal of Medicine, Vol. 360, 2009, pp. 1526-1538.
doi:10.1056/NEJMra0800028