Guidelines for the Treatment of Myocarditis
Acute viral myocarditis: Epidemiology and pathophysiology
Lara Shekerdemian, MD, MRCP; Desmond Bohn, MB, MRCP
KEY WORDS: acute viral myocarditis; epidemiology; pathophysiology
A cute viral myocarditis should
be suspected in any child pre-
senting in cardiac failure with
a structurally normal heart
without a history of heart disease. It
should also be considered in the differen-
tial diagnosis of sudden death in previ-
ously healthy neonates and older chil-
dren. A confirmatory diagnosis can only
be made on the basis of histology show-
ing lymphocytic infiltration of the myo-
cardium together with myocyte necrosis
(Dallas criteria). If myocardial tissue is
not available, a clinical history of heart
failure, together with polymerase chain
reaction (PCR) for known viral patho-
gens, is a secondary option. The objec-
tives for treatment are to maintain car-
diac output and oxygen delivery while
minimizing myocardial injury. Long-
term outcome is good in those children
who survive the initial period of acute
cardiovascular instability.
Overview
Acute viral myocarditis is an impor-
tant cause of cardiac morbidity and mor-
tality in infants and children, and there is
increasing evidence to suggest that it is a
major cause of sudden, unexpected death
in this population. The presentation of
acute viral myocarditis can vary from a
mild viral illness with subclinical myo-
cardial inflammation to acute collapse
and sudden death in a previously healthy
child. Originally, the term myocarditis
was used to describe an acute inflamma-
tory disease of the myocardium, usually
From the Pediatric Intensive Care Unit, Royal Chil-
drens’ Hospital, Melbourne, Australia (LS); the Depart-
ment of Critical Care Medicine, Hospital for Sick Chil-
dren, Toronto, Ontario, Canada (DB); and the
Department of Anesthesia, University of Toronto, On-
tario, Canada (DB).
Copyright © 2006 by the Society of Critical Care
Medicine and the World Federation of Pediatric Inten-
sive and Critical Care Societies
DOI: 10.1097/01.PCC.0000244338.73173.70
S2
caused by viral infection. We now know
that myocarditis and dilated cardiomyop-
athy (DCM) represent a spectrum of dis-
ease, and there is considerable overlap
between the two. However, the distinc-
tion between the two is further blurred by
the lack of specific diagnostic criteria
and, often, the limited availability of a
confirmatory tissue diagnosis. Moreover,
it is becoming increasingly clear that the
application of the adult classification to
this disease spectrum may not always be
appropriate in children and can lead to
confusion regarding overall prognosis.
An outline classification is provided in
Table 1. We recognize that the distinction
between acute viral myocarditis and DCM
is sometimes difficult in the absence of
confirmatory histology, and therefore,
there may be some crossover between the
two in this and the other reviews that
follow. We do not propose to discuss in
detail entities such as eosinophilic and
giant cell myocarditis. These are impor-
tant causes of myocarditis and DCM in
adults, but they are rare in children.
Much of our early knowledge of the
pathophysiology of acute viral myocardi-
tis comes from postmortem studies in
adults. More recently, our understanding
of the disease has improved, based on
animal models, the increased use of en-
domyocardial biopsy, and the advent of
accurate and rapid diagnostic techniques,
including PCR. This review will focus on
the epidemiology and pathophysiology of
acute viral myocarditis in children and
serve as the background for the evidence-
based reviews that follow.
Process
MEDLINE database searches were
conducted to find published data regard-
ing the epidemiology of acute viral myo-
carditis in children. We also reviewed
publications on sudden death in children.
The search strategy used was similar in
this and the subsequent evidence-based
Pediatr Crit Care Med 2006 Vol. 7, No. 6 (Suppl.)
guideline articles in this issue of Pediat-
ric Critical Care Medicine. The template
used for assessing the level of evidence
and the recommendations follows a sim-
ilar format used for traumatic brain in-
jury in children (1).
Scientific Foundation
Clinical Presentation. A diagnosis of
acute viral myocarditis depends on a clin-
ical history, together with a confirmatory
tissue diagnosis or evidence of viral infec-
tion. The diagnosis and histologic classi-
fication of myocarditis has traditionally
been made from endomyocardial biopsy,
using the widely accepted Dallas criteria
(2). This focuses on the degree of myo-
cardial inflammation, myocyte degenera-
tion or necrosis, cellular infiltrate, and
fibrosis (Table 2). The Dallas criteria
alone cannot confirm (or exclude) the
presence of viral infection; thus, the im-
mediate investigations must also include
an exhaustive search for evidence of viral
involvement.
Acute viral myocarditis in children
frequently has an insidious disease onset
with a recent history of a nonspecific viral
illness, associated with abdominal pain,
nausea and vomiting, or coryzal symp-
toms. This can result in a diagnosis of
gastroenteritis or an upper respiratory in-
fection in young children. Cardiovascular
signs are often quite subtle and include
tachycardia, mild hypotension, or unex-
plained metabolic acidosis. Other pre-
senting symptoms include syncope (due
to heart block or other arrhythmias),
chest pain in adolescents and young
adults (3), pulmonary edema, and con-
gestive heart failure. However, in many
instances, the cardiovascular symptoms
are minimal, and because of the robust
physiology in children with their ability
to compensate for decreased heart func-
tion, the diagnosis may not even be sus-
pected until acute collapse or sudden
death occurs. More detailed investiga-
Table 1. Classification of myocarditis based on clinical presentation, history, and histopathology

Type Features and Clinical Presentation Histologic Features Outcome

Fulminant Short viral prodrome Lymphocytic infiltration Death or survival with

myocarditis Cardiogenic shock Myocyte necrosis normal myocardial
Heart block or ventricular ⫾Myocyte degeneration function
arrhythmias May need mechanical
Sudden death support
Normal heart size on chest
radiography
Reduced LV function
Subacute or chronic Viral prodrome Lymphocytic infiltration ⫾ May go on to develop dilated
myocarditis Heart failure myocyte necrosis cardiomyopathy
Cardiomegaly on chest radiography Known as chronic active when
May have subclinical presentation there is no myocyte necrosis
Echocardiography: Reduced LV
function
Dilated Congestive heart failure ⫾ history Myocyte hypertrophy, myofibrillar Chronic heart failure ⫾
cardiomyopathy of viral illness loss transplantation
Cardiomegaly Interstitial fibrosis; minimal or no 60% 5-yr survival
LV dysfunction inflammation
May have family history

LV, left ventricular.

Table 2. Dallas criteria for diagnosis of myocar-
ditis
● General definition: Myocardial cell injury
with degeneration or necrosis with
inflammatory infiltrate not caused by
ischemia
● Active myocarditis: Both myocyte
degeneration or necrosis and definite cellular
infiltrate (usually lymphocytes) with or
without fibrosis
● Borderline myocarditis: Definite cellular
infiltrate without myocyte injury
● Persistent myocarditis: Continued active
myocarditis on repeat myocardial biopsy
● Resolving/resolved myocarditis: Diminished
or absent infiltrate with evidence of
connective tissue healing
tions on presentation may reveal reduced
ventricular function on echocardiogram
and abnormal electrocardiogram (includ-
ing ST-T changes, low-voltage complexes,
or arrhythmias). A chest radiograph may
show a normal-sized heart or mild car-
diomegaly with increased pulmonary vas-
cular markings. A more detailed evi-
dence-based review of establishing a
diagnosis will follow.
Incidence of Acute Viral Myocarditis.
The true incidence of acute viral myocar-
ditis in children is likely to be higher
than generally quoted because of the rel-
ative lack of symptoms relating to the
heart and a significant number of sub-
clinical presentations that are simply di-
agnosed as “the flu.” There are also likely
a significant number of missed diagnoses
because of incomplete investigations of
cases of sudden death, especially in young
children.
Acute viral myocarditis, however, is
one of the commonest causes of sudden
cardiac death in children without previ-
ously diagnosed heart disease (4 – 8).
Wren et al. (9) reviewed 270 children and
adolescents 1–20 yrs of age who died sud-
denly during a 10-yr period in the north
of England. A total of 26 had previously
unsuspected heart disease, and five of
these (17%) had acute viral myocarditis.
However, this study only included deaths
that occurred outside the hospital or in
the emergency department and excluded
patients who died ⬎24 hrs after admis-
sion and is therefore likely to be an un-
derestimate. Another interesting feature
of this study is that 11% of deaths in
these children remained unexplained, de-
spite a full autopsy examination. This is
not an uncommon feature of postmortem
studies in children who die unexpectedly,
with a surprisingly high number of cases
in which “no anatomical cause of death”
or “cause unknown” is the pathologist’s
conclusion.
A more diligent search for histologic
abnormalities in the myocardium to-
gether with the introduction of more so-
phisticated viral diagnostic tests may re-
sult in a reduction of the number of cases
of so-called “sudden and unexplained”
deaths in children and an apparent in-
crease in the incidence of acute viral
myocarditis. A study by Steinberger et al.
(8) from a single institution that reported
on cardiac deaths during a 25-yr period
found 14 of 50 patients with postmortem
findings consistent with acute viral myo-
carditis in the age group of 1–21 yrs. This
incidence is similar to that reported in
the study by Wren et al (9). Studies from
Sweden and Italy of patients up to 35 yrs
of age with sudden cardiac death have
estimated that 10% are due to acute viral
myocarditis (10, 11). Postmortem histol-
ogy showing evidence of acute viral myo-
carditis without clinical symptoms has
also been found in association with sud-
den and unexplained death during anes-
thesia for minor surgical procedures (5)
and drowning accidents in children who
were competent swimmers (12).
Acute viral myocarditis as a diagnosis
has also come to the fore in the investi-
gation of deaths in children of ⬍1 yr of
age for whom there is no anatomical
cause of death. In these cases, negative
autopsy findings are frequently taken to
imply a diagnosis of sudden infant death
syndrome. In a retrospective series of 20
infant deaths that were initially consid-
ered as sudden infant death syndrome,
Dettmeyer et al. (13) found that although
only one had acute viral myocarditis by
Dallas criteria (lymphocytic infiltration
and myocyte necrosis), in a further nine
cases the diagnosis was suspected based
on immunohistochemistry analysis look-
ing for antigens and T-lymphocyte mark-
ers. In a further prospective study by the
same group (14) that analyzed 62 infants
with suspected sudden infant death syn-

Pediatr Crit Care Med 2006 Vol. 7, No. 6 (Suppl.) S3

Table 3. Viral pathogenesis of acute myocarditis in children
Estimated
Causes Prevalencea
Common
Adenovirus 55–60%
Coxsackievirus 30–35%
Uncommon
Parvovirus B19 1–2%
Influenza A/B ⬍15%
Herpes simplex
Epstein-Barr
Cytomegalovirus
PCR, polymerase chain reaction; LV, left ventricular.
a
Indicates proportions of virus-positive samples (27, 28).
drome and 11 controls and included both
PCR for viruses and immunohistochem-
istry, 26 infants were found to be positive
for viral disease (enterovirus, n ⫽ 14;
adenovirus, n ⫽ 2; Epstein-Barr virus, n
⫽ 3; parvovirus, n ⫽ 7). Grangeot-Keros
et al. (15), in a study of 33 infants with
sudden death, found that 50% of those
with a history of viral illness were positive
for enterovirus either by PCR or immu-
noglobulin M antibody assay. These data,
together with reports in neonates of car-
diogenic shock and ischemic changes on
electrocardiogram associated with PCR
studies positive for enterovirus (16), raise
the possibility that acute viral myocardi-
tis is a much more common underlying
cause of death in the first year of life than
previously suspected.
Outside of a presentation of sudden
death, two large epidemiologic studies of
cardiomyopathy in children published in
2003 from different parts of the world
give some important insights into the
incidence of this disease. The first, from
Australia, reported an incidence of car-
diomyopathy 1.24 per 100,000 in children
⬍10 yrs of age during a 10-yr period (17).
Of these, 25 of 187 (14%) were classified
as DCM due to acute viral myocarditis,
confirmed at either biopsy or autopsy.
The second study was from two regions of
the United States and included children
S4
Comments
Can be identified by PCR on tracheal
aspirates.
Frequently identified in association
with mild or borderline
myocarditis.
Previously thought to be the
commonest viral pathogen.
Late persistence of virus seen in
patients with cardiomyopathy.
Associated with fulminant
myocarditis and sudden death in
all ages.
Implicated in pathogenesis of
“idiopathic” LV dysfunction in
adults.
? Increasing prevalence or improved
viral diagnostics
1–18 yrs of age, with data collected dur-
ing a 4-yr period (18). The incidence of
cardiomyopathy was 1.13 per 100,000,
with a confirmatory diagnosis of acute
viral myocarditis made in 21 of 239 chil-
dren with DCM (9%). The number of
cases with a histologic diagnosis was not
specified. There are important differences
in these two studies in terms of age of
patients enrolled and the criteria for di-
agnosis of acute viral myocarditis that
may not make them comparable. That
notwithstanding, it would a be reasonable
assumption that ⱖ10% of children pre-
senting with heart failure and DCM will
have an underlying viral pathogenesis.
However, this may be an underestimate
because of the lack of biopsy confirma-
tion of the diagnosis in many cases and
an unknown number of subclinical cases.
It should also be noted that the diagnosis
can be missed at endomyocardial biopsy,
even when the standard five to six sam-
ples are taken from the right ventricle
(19). In the absence of biopsy material to
confirm the diagnosis, the use of PCR on
tracheal aspirates has been shown to have
a high yield for viral identification, par-
ticularly adenovirus (20). This, together
with findings of heart failure and ventric-
ular dilation, is highly indicative of acute
viral myocarditis.
Pediatr Crit Care Med 2006 Vol. 7, No. 6 (Suppl.)
Genetic Predisposition
Increased susceptibility to myocardial
involvement in coxsackie-
adenovirus receptor
(CAR)—positive hearts. May be
familial.
1. CAR—positive hearts
2. Dystrophin-deficient individuals
Pathophysiology of Acute Viral Myo-
carditis. Viral infections are responsible
for the majority of cases of acute myocar-
ditis (21–27). This has been difficult to
prove in the past because viral particles
were rarely seen in the myocardium ei-
ther at the time of biopsy or autopsy.
Thus, the diagnosis of acute viral myo-
carditis was previously reliant on the Dal-
las criteria, with supportive evidence
from viral cultures or serology. However,
during the past decade, the introduction
of PCR has provided us with a rapid and
reliable means of identifying viral infec-
tion in the presence or absence of clear-
cut inflammatory change (28). The vi-
ruses implicated in causing acute viral
myocarditis are outlined in Table 3.
In the largest published series investi-
gating a viral cause for biopsy- or autop-
sy-proven acute viral myocarditis, Bowles
et al. (29) reported on 624 patients, to-
gether with a further 149 with DCM, and
included 177 adults and 596 children.
There were also controls without heart
disease. Viral genome was amplified us-
ing PCR in samples of 38% of patients
with acute viral myocarditis and 20%
with DCM. The commonest virus identi-
fied in patients with acute viral myocar-
ditis of all ages was adenovirus (23%),
and enterovirus was found in 14%. Other
interesting findings from this study were
Figure 1. Time course of viral myocarditis based on an animal experimental model. Reproduced with permission from Feldman AM, McNamara D:
Myocarditis. N Engl J Med 2000; 343:1388 –1398.
the high mortality, especially in new-
borns and infants, and the number of
patients surviving with poor function.
This is in contrast to other studies that
show good long-term recovery of func-
tion in critically ill children with acute
viral myocarditis, including those who
survived with the use of mechanical sup-
port (30, 31).
The apparent contrast in survival and
difference in subsequent cardiac function
has led to the classification of acute viral
myocarditis into fulminant variety with a
very acute onset and the requirement for
inotropic or mechanical support vs. an
acute (nonfulminant) variety with a
longer prodrome for those who do not
present so acutely ill (32). The differences
between these two groups was contrasted
in a large study of 147 adult patients
(⬎15 yrs old) with biopsy-proven disease.
The 15 patients with acute viral myocar-
ditis had more severe disease by histology
(lymphocytic infiltration with myocyte
necrosis as opposed to no necrosis) and
more severe hemodynamic compromise.
Despite this, 93% of the fulminant group
were alive without transplant up to 11 yrs
after biopsy (average follow-up, 5 yrs)
compared with only 45% in the nonful-
minant group. One could speculate that
the patients in the fulminant group have
Pediatr Crit Care Med 2006 Vol. 7, No. 6 (Suppl.)
a short-lived and more intense inflamma-
tory response to viral infection of the
myocardium that then recovers with sup-
portive measures in contrast to those
with the nonfulminant variety in which
the inflammation is less intense but the
virus persists in a more indolent form,
with progression to a chronic cardiomy-
opathy. There is some evidence that acute
viral myocarditis due to adenovirus is as-
sociated with a less fulminant “acute” dis-
ease, in terms of both the clinical presen-
tation and the histopathologic
inflammatory response, than that seen
with enterovirus (33).
Immune Response to Viral Infection. Vi-
ral exposure leads to an acute or subacute
immune response that is responsible for
most of the inflammation, infiltration,
and myocardial damage that ensue. Much
of our knowledge of this process comes
from animal models, particularly the
mouse, exposed to coxsackievirus and is
summarized in Figure 1. Ribonucleic
acid viral protein enters the myocytes,
causing some myocyte necrosis and infil-
tration with inflammatory cells. This ini-
tial phase lasts 4 days, and during this
time, virus can be identified in the myo-
cardium. After this, there is invasion by
macrophages, natural killer cells, and T
cells, and it is these latter that are re-
sponsible for the inflammatory response
and myocardial damage. Macrophage ac-
tivation also results in the release of cy-
tokines, including interleukin-1, inter-
leukin-2, tumor necrosis factor,
interferon-␥, and nitric oxide. Tumor ne-
crosis factor in particular, and also acti-
vating endothelial cells and recruiting in-
flammatory cells, have potent negative
inotropic effects. Inducible nitric oxide
synthase activity appears on day 4 and
peaks at day 8. There is a complex balance
between proinflammatory cytokines such
as tumor necrosis factor and interfer-
on-␥, and interleukin-10 and interleu-
kin-2 have been shown to protect animals
from myocardial damage.
Spectrum of Acute Viral Myocarditis:
The Role of Viral Infection in DCM. There
is increasing evidence to suggest that
there is an association between viral in-
fection of the myocardium or “idiopathic”
(nonischemic) DCM and isolated left ven-
tricular dysfunction. In the series by
Bowles et al. (29), 20% of patients with
DCM tested positive on PCR amplification
of viral genome. Three fifths of these had
adenovirus, and the remainder had en-
terovirus. In another series of adults with
isolated left ventricular dysfunction, 30%
of myocardial biopsies were positive for
S5
viral PCR, with equal proportions with
adenovirus or enterovirus (34, 35).
Interesting new insights into the viral
pathogenesis of acute viral myocarditis
and the role of viral infection in the de-
velopment of DCM have come from re-
cent studies that have examined the myo-
cardial cytoskeleton in patients with
DCM. In 1997, a common coxsackie B-
adenovirus receptor was identified (36)
that binds both coxsackie B and group C
adenoviruses. The increased expression of
coxsackie B-adenovirus receptor has been
found in patients with DCM compared
with normal hearts, and there is evidence
to suggest that this may be familial (37).
Badorff et al. (38) recently demonstrated
that coxsackie B3 protease can cleave the
cytoskeletal protein dystrophin, a finding
in patients with cardiomyopathy associ-
ated with Duchenne muscular dystrophy.
Furthermore, these investigators have
shown a more severe cardiomyopathy and
increased viral replication in dystrophin-
deficient mice infected with enterovirus
(39). This raises the possibility that some
individuals, deficient in dystrophin, may
be predisposed to develop DCM after an
enteroviral infection. These factors would
also offer an explanation as to why the
same viral infection will result in a self-
limiting viral illness in one individual but
catastrophic myocardial damage in an-
other.
Summary
Acute viral myocarditis represents a
complex disease spectrum. Although our
management, even in 2006, remains sup-
portive, during the past decade, a number
of important developments have provided
important insights into the pathophysiol-
ogy of this disease. In particular, the
more routine use of endomyocardial bi-
opsy where appropriate and an early, ex-
haustive search for viruses that includes
PCR amplification have improved our di-
agnostic capabilities.
Key Elements for Future
Research
The molecular and genetic basis of
viral myocardial cytopathy represents an
exciting area of research that will im-
prove our understanding of the predispo-
sition to acute viral myocarditis and may
provide us with targets for the future
prevention and treatment of this chal-
lenging disease.
S6
REFERENCES
1. Adelson PD, Bratton SL, Carney NA, et al:
Guidelines for the acute medical manage-
ment of severe traumatic brain injury in in-
fants, children, and adolescents. Chapter 1:
Introduction. Pediatr Crit Care Med 2003;
4(3 Suppl):S2–S4
2. Aretz HT, Billingham ME, Edwards WD, et al:
Myocarditis: A histopathologic definition and
classification. Am J Cardiovasc Pathol 1987;
1:3–14
3. Karjalainen J, Heikkila J: Incidence of three
presentations of acute myocarditis in young
men in military service: A 20-year experi-
ence. Eur Heart J 1999; 20:1120 –1125
4. Corrado D, Basso C, Thiene G: Sudden car-
diac death in young people with apparently
normal heart. Cardiovasc Res 2001; 50:
399 – 408
5. Forcada P, Beigelman R, Milei J: Inapparent
myocarditis and sudden death in pediatrics:
Diagnosis by immunohistochemical staining
[letter]. Int J Cardiol 1996; 56:93–97
6. Noren GR, Staley NA, Bandt CM, et al: Oc-
currence of myocarditis in sudden death in
children. J Forensic Sci 1977; 22:188 –196
7. Smith NM, Bourne AJ, Clapton WK, et al:
The spectrum of presentation at autopsy of
myocarditis in infancy and childhood. Pa-
thology 1992; 24:129 –131
8. Steinberger J, Lucas RV Jr, Edwards JE, et al:
Causes of sudden unexpected cardiac death
in the first two decades of life. Am J Cardiol
1996; 77:992–995
9. Wren C, O’Sullivan JJ, Wright C: Sudden
death in children and adolescents. Heart
2000; 83:410 – 413
10. Basso C, Corrado D, Thiene G: Cardiovascu-
lar causes of sudden death in young individ-
uals including athletes. Cardiol Rev 1999;
7:127–135
11. Wisten A, Forsberg H, Krantz P, et al: Sud-
den cardiac death in 15–35-year olds in Swe-
den during 1992–99. J Intern Med 2002; 252:
529 –536
12. Somers GR, Smith CR, Wilson GJ, et al:
Association of drowning and myocarditis in a
pediatric population: An autopsy-based
study. Arch Pathol Lab Med 2005; 129:
205–209
13. Dettmeyer R, Schlamann M, Madea B: Im-
munohistochemical techniques improve the
diagnosis of myocarditis in cases of suspected
sudden infant death syndrome (SIDS). Fo-
rensic Sci Int 1999; 105:83–94
14. Dettmeyer R, Baasner A, Schlamann M, et al:
Role of virus-induced myocardial affections
in sudden infant death syndrome: A prospec-
tive postmortem study. Pediatr Res 2004;
55:947–952
15. Grangeot-Keros L, Broyer M, Briand E, et al:
Enterovirus in sudden unexpected deaths in
infants. Pediatr Infect Dis J 1996; 15:
123–128
16. Inwald D, Franklin O, Cubitt D, et al: Entero-
virus myocarditis as a cause of neonatal col-
Pediatr Crit Care Med 2006 Vol. 7, No. 6 (Suppl.)
lapse. Arch Dis Child Fetal Neonatal Ed
2004; 89:F461–F462
17. Nugent AW, Daubeney PE, Chondros P, et al:
The epidemiology of childhood cardiomyop-
athy in Australia. N Engl J Med 2003; 348:
1639 –1646
18. Lipshultz SE, Sleeper LA, Towbin JA, et al:
The incidence of pediatric cardiomyopathy in
two regions of the United States. N Engl
J Med 2003; 348:1647–1655
19. Chow LH, Radio SJ, Sears TD, et al: Insensi-
tivity of right ventricular endomyocardial bi-
opsy in the diagnosis of myocarditis. J Am
Coll Cardiol 1989; 14:915–920
20. Akhtar N, Ni J, Stromberg D, et al: Tracheal
aspirate as a substrate for polymerase chain
reaction detection of viral genome in child-
hood pneumonia and myocarditis. Circula-
tion 1999; 99:2011–2018
21. Beghetti M, Gervaix A, Haenggeli CA, et al:
Myocarditis associated with parvovirus B19
infection in two siblings with merosin-
deficient congenital muscular dystrophy.
Eur J Pediatr 2000; 159:135–136
22. Fujiwara M, Shimozono H, Ono H, et al:
Polyclonal proliferation of lymphocytes con-
taining the Epstein-Barr virus genome in a
patient dying of myocarditis in chronic active
Epstein-Barr virus infection. J Pediatr He-
matol Oncol 2003; 25:85– 88
23. Ishikawa T, Zhu BL, Li DR, et al: Epstein-
Barr virus myocarditis as a cause of sudden
death: Two autopsy cases. Int J Legal Med
2005; 119:231–235
24. Matsumori A, Yutani C, Ikeda Y, et al: Hep-
atitis C virus from the hearts of patients with
myocarditis and cardiomyopathy. Lab Invest
2000; 80:1137–1142
25. Nigro G, Bastianon V, Colloridi V, et al: Hu-
man parvovirus B19 infection in infancy as-
sociated with acute and chronic lymphocytic
myocarditis and high cytokine levels: Report
of 3 cases and review. Clin Infect Dis 2000;
31:65– 69
26. Nolte KB, Alakija P, Oty G, et al: Influenza A
virus infection complicated by fatal myocar-
ditis. Am J Forensic Med Pathol 2000; 21:
375–379
27. Rohayem J, Dinger J, Fischer R, et al: Fatal
myocarditis associated with acute parvovirus
B19 and human herpesvirus 6 coinfection.
J Clin Microbiol 2001; 39:4585– 4587
28. Martin AB, Webber S, Fricker FJ, et al: Acute
myocarditis: Rapid diagnosis by PCR in chil-
dren. Circulation 1994; 90:330 –339
29. Bowles NE, Ni J, Kearney DL, et al: Detection
of viruses in myocardial tissues by polymer-
ase chain reaction: Evidence of adenovirus as
a common cause of myocarditis in children
and adults. J Am Coll Cardiol 2003; 42:
466 – 472
30. Duncan BW, Bohn DJ, Atz AM, et al: Mechan-
ical circulatory support for the treatment of
children with acute fulminant myocarditis.
J Thorac Cardiovasc Surg 2001; 122:
440 – 448
31. Lee KJ, McCrindle BW, Bohn DJ, et al: Clin-
ical outcomes of acute myocarditis in child-
hood. Heart 1999; 82:226 –233
32. Lieberman EB, Hutchins GM, Herskowitz A,
et al: Clinicopathologic description of myo-
carditis. J Am Coll Cardiol 1991; 18:
1617–1626
33. Felker GM, Boehmer JP, Hruban RH, et al:
Echocardiographic findings in fulminant and
acute myocarditis. J Am Coll Cardiol 2000;
36:227–232
34. Kuhl U, Pauschinger M, Noutsias M, et al:
High prevalence of viral genomes and mul-
tiple viral infections in the myocardium of
Pediatr Crit Care Med 2006 Vol. 7, No. 6 (Suppl.)
adults with “idiopathic” left ventricular dys-
function. Circulation 2005; 111:887– 893
35. Kuhl U, Pauschinger M, Seeberg B, et al:
Viral persistence in the myocardium is asso-
ciated with progressive cardiac dysfunction.
Circulation 2005; 112:1965–1970
36. Bergelson JM, Cunningham JA, Droguett G,
et al: Isolation of a common receptor for
Coxsackie B viruses and adenoviruses 2 and
5. Science 1997; 275:1320 –1323
37. Noutsias M, Fechner H, de Jonge H, et al:
Human coxsackie-adenovirus receptor is
colocalized with integrins alpha(v) beta(3)
and alpha(v) beta(5) on the cardiomyocyte
sarcolemma and upregulated in dilated
cardiomyopathy: Implications for cardio-
tropic viral infections. Circulation 2001;
104:275–280
38. Badorff C, Lee GH, Lamphear BJ, et al: En-
teroviral protease 2A cleaves dystrophin: Ev-
idence of cytoskeletal disruption in an ac-
quired cardiomyopathy. Nat Med 1999;
5:320 –326
39. Xiong D, Lee GH, Badorff C, et al: Dystrophin
deficiency markedly increases enterovirus-
induced cardiomyopathy: A genetic predispo-
sition to viral heart disease. Nat Med 2002;
8:872– 877
S7