803

STUDENTS CORNER
REVIEW ARTICLE
Management of acute myocarditis in children
Quratulain Merchant,1 Anwarul Haque,2 Babar Sultan Hasan3

Abstract Myocarditis can be regarded as a precursor to dilated

Myocarditis is defined as the inflammation of the cardiomyopathy (DCM), which is the most frequent cause
myocardium. It continues to be a significant cause of of heart transplantation.5,6 Endomyocardial biopsy (EMB),
morbidity and mortality in the paediatric population and tissue histology using the 'Dallas criteria' and
is the commonest cause of cardiac failure in a healthy immunological staining may still be the definitive test for
child. Some studies estimate the incidence of myocarditis diagnosing myocarditis.7,8 The mainstay of treatment is
to be around 1 per 100 000. PubMed search was supportive and symptom-based care, though
performed using the term 'myocarditis.' The search was mechanism-based therapy has its role in specific cases of
limited to age 0-19 years. A total of 50 articles were myocarditis.9
identified between 1966 to date and reviewed.
Myocarditis is a challenging diagnosis to make on clinical
Aetiology
grounds and requires high index of suspicion. The A broad array of infectious, immune-mediated and drug
cornerstone of treatment remains supportive though hypersensitivity causes are implicated in cases of
therapeutic modalities such as immunosuppressive and myocarditis (Table-1). Out of these, majority of the cases
intravenous immunoglobulin therapies are being studied
extensively. The overall prognosis of the disease is good Table-1: Causative agents of myocarditis in children.
with survival rates up to 80%.
Infectious Schistosomiasis
Keywords: Myocarditis, Paediatric population, PubMed.
Viruses
Introduction Coxsackie B Immune-mediated
Myocarditis, or inflammatory cardiac myopathy, is defined Adenovirus SLE (Systemic Lupus Erythematosus)
Echovirus Rheumatic fever
as the inflammation of the myocardium in association
Hepatitis virus Rheumatoid arthritis
with myocellular necrosis and degeneration.1 It can either Herpes simplex virus Inflammatory bowel disease
be focal or diffuse and can lead to cardiac dysfunction. Epstein Bar virus Sarcoidosis
Myocarditis continues to be a significant cause of Parvovirus Churg-Struss syndrome
morbidity and mortality in the paediatric population and HIV Diabetes mellitus
is the commonest cause of cardiac failure in a healthy Influenza virus Thyrotoxicosis
child.2 Sub-clinical presentation of the disease leading to Poliomyelitis Wegner's disease
under-diagnosis makes it difficult to determine the true Mumps
incidence of myocarditis. However, it accounts for 12% of Rubella
Bacteria
sudden cardiac deaths in adolescents and young adults.3
Streptococcus Toxic/Hypersensitivity
The clinical presentation of myocarditis has a broad Mycoplasma bacteria Amphotericin B
spectrum of signs and symptoms as it varies from Legionella Tetracyclines
Treponema pallidum Sulfonamides
asymptomatic cases to complete cardiovascular collapse
Mycobacterium species Diuretics
(referred to as acute fulminant myocarditis).4 The main Rickettsial Cephalosporin
causative agent is a virus, Coxsackie type B virus being the Rickettsia rickettsii Cyclophosphamide
most common, but it can also be due to bacterial infections, Fungi Ethanol
immune-mediated and toxic/hypersensitivity reactions.2,3 Candida Heavy metals
Histoplasma Cocaine
Cryptococcus Anthracycline
1Medical Student, Aga Khan University Medical College, 2,3Department of Protozoal/Parasites
Paediatrics and Child Heath, Aga Khan University, Karachi, Pakistan. Trypanosoma cruzi
Correspondence: Babar Sultan Hasan. Email: [email protected] Toxocara canis

Vol. 63, No. 6, June 2013

804 Q. Merchant, A. Haque, B. S. Hasan

in the paediatric population are caused by viral infections Pathogenesis

like Adenovirus, Epstein-Barr virus and, most importantly, The progression of myocarditis, as demonstrated by
Coxsackie virus type B.3 However, with the advent of Murine models,5 can be divided into three recognised
newer diagnostic modalities, including polymerase chain phases: an acute phase caused by direct cellular damage
reaction (PCR) and EMB, Parvovirus B19 and Human by the infectious agent; a sub-acute phase which involves
Herpes Virus 6 were also detected in a number of patients innate host immune response against virus infested cells;
with biopsy-proven myocarditis in European studies.10 and chronic phase which leads to DCM.1,5
Although myocarditis is a very common cardiac
pathological autopsy finding in adult patients diagnosed The acute phase is characterised by direct myocellular
with human immunodeficiency virus (HIV) (up to 50-70% invasion by cardiotropic viruses via receptor-mediated
of the cases),11 it remains uncommon among HIV-infected endocytosis and rapid viral replication, leading to
children. In these patients, cytomegalovirus and myocellular necrosis and apoptosis.3 A specific Coxsackie
adenovirus are found in histologically-proven virus-Adenovirus Receptor (CAR), member of the
myocarditis, raising the question whether HIV or immunoglobulin superfamily, appears to mediate this
secondary viruses are the culprits behind high incidence attachment in cases of viral myocarditis caused by
of myocarditis in an immunocompromised host.8 Coxsackie virus and Adenovirus. The expressions of these
Moreover, in the developing world, mumps, poliomyelitis receptors therefore determine an individual's
and rubella may be the other contributing organisms susceptibility to viral myocarditis. The acute phase lasts
leading to the development of myocarditis, especially in only a few days (Figure-1).
unvaccinated children. The acute phase is followed by rapid progression to host's

Figure-1: Time line of Viral Myocarditis (days). DCM: Dilated cardiomyopathy.

J Pak Med Assoc

Management of acute myocarditis in children 805
immune cascade, known as the sub-acute phase of the Table-2: Clinical presentation of myocarditis in different age groups.
disease. Macrophage activation, due to cardiotropic
Neonates Nonspecific signs: fever, irritability, pallor,
viruses, leads to production of inflammatory cytokines,
poor feeding
interleukin 1β (IL1β), IL2 and tumour necrosis factor-alpha Ominous signs: apnoea, episodic cyanosis
(TNF-α), which cause recruitment of T lymphocytes and Young children and adolescents Nonspecific signs: fever, myalgia, coryza,
natural killer (NK) cells. The T lymphocytes play a pivotal anorexia, vomiting
role in this immune cascade by targeting the myocardium Atypical signs: seizures, syncope, sudden
by molecular mimicry, causing further myocardial cardiac death
damage.12 Both cell-mediated immunity and humoral
immunity play a role in this phase of the disease. In
addition to production of pro-inflammatory cytokines, symptoms like fever, irritability, pallor and poor feeding,
titres of protective anti-inflammatory cytokines also rise, indicating an infection.7 However, neonates may also
present with ominous signs such as apnoea and episodic
suggesting interplay between pro- and anti-inflammatory
cyanosis.7
cytokines13 during this phase of myocarditis. It has also
been found that sub-acute phase is the most destructive Signs and symptoms of myocarditis are also variable in
phase of myocarditis and can last from a few weeks to older children. They may present with non-specific upper
several months. Decrease in viral load in this phase is respiratory or gastrointestinal symptoms, fever, myalgia,
associated with recovery of left ventricular (LV) function.5 coryza, anorexia and vomiting.7 Chest pain, due to
pericardial irritation, is non-specific and is only reported in
In majority of the cases where insult to myocardium is
minority of the cases.2,7 Myocarditis may also present with
limited, the heart function recovers within a few months,
atypical features such as syncope and seizures and
but in cases with more extensive myocardial insult,
accounts for 12% of sudden cardiac deaths in adolescents
chronic myocarditis may develop. This third phase of the
and young adults.3
disease, the chronic phase, is characterised by myocardial
fibrosis and development of DCM.1 This involves chamber Owing to non-specific symptoms in majority of cases, the
dilation and ventricular wall thinning with impairment of diagnosis of myocarditis is difficult to make on clinical
the contractile function of the heart, leading to grounds, leading to missed diagnosis in up to 83% of the
permanent damage with scar tissue replacing the cases on the first presentation to a medical provider.18
necrotic myocardium.2 Generally, medical practitioners become suspicious of
myocarditis when there is tachycardia in an otherwise
Clinical Presentation healthy child without a clearly defined cause i.e. fever or
The clinical presentation of myocarditis has a broad dehydration.
spectrum of signs and symptoms as it varies from
asymptomatic cases to mild lethargy, dysrhythmias, Patients who have developed high degree of cardiac
complete cardiovascular collapse and death.4,10 dysfunction and congestive heart failure (CHF), present
Myocarditis can be broadly divided into fulminant, acute with signs and symptoms of respiratory distress,
and chronic presentation.14 Fulminant myocarditis is diaphoresis, tachycardia, tachypnoea, gallop rhythm,
characterised by sudden onset of severe haemodynamic decreased peripheral pulses and hepatomegaly. A gallop
compromise following a viral infection. Though more rhythm, produced by the third or fourth heart sound is
dramatic in its presentation, if managed aggressively with best heard at the apex. The first sign of CHF appreciated in
early mechanical support using extracorporeal children is eyelid puffiness due to fluid retention.2
membrane oxygenator (ECMO), fulminant myocarditis Differential Diagnosis
patients may have full recovery and less risk of developing Other diseases that can mimic myocarditis are sepsis,
DCM.15 Acute myocarditis follows a less distinct onset, dilated cardiomyopathy secondary to metabolic disorders
initially with less severe compromise, but may lead to or idiopathic dilated cardiomyopathy or anomalous left
worse outcome than fulminant myocarditis, with the coronary artery off the pulmonary artery (ALCAPA).
development of DCM. D'Ambrosio et al showed that 21%
of diagnosed cases of acute myocarditis developed DCM Diagnostic Modalities
over a mean follow-up of 3 years.16 Chronic myocarditis The chest x-ray typically demonstrates cardiomegaly and
can be labelled so if it persists for more than 3 months.17 increased pulmonary vascular markings, indicating
pulmonary oedema.
Clinical presentation also varies in different age groups
(Table-2).7 Neonates usually present with non-specific The 12-lead electrocardiogram (ECG) is used widely in the

Vol. 63, No. 6, June 2013

806 Q. Merchant, A. Haque, B. S. Hasan

diagnosis of myocarditis despite low sensitivity.5,19 The

most common ECG changes are sinus tachycardia, S-T
wave changes, low voltage QRS complexes, axis deviation
and ventricular hypertrophy.2 Infarction patterns, atrial
abnormalities and various degrees of heart block may also
be seen.20 The presence of Q waves, a new left bundle
branch block and prolonged QRS duration of >120msec is
associated with higher rates of cardiac death or heart
transplantation and may be used as a prognostic
indicator.5
Echocardiogram is essential in diagnosis, treatment and
follow-up of patients with myocarditis.2 It does not show
any specific features of myocarditis, but helps in ruling out
other cardiac abnormalities such as valvular heart disease
or other cardiomyopathies (hypertrophic or restrictive
cardiomyopathy).2 Durani at el recently reported that
echocardiography will show abnormal findings in 98% of
paediatric myocarditis, with segmental wall motion
abnormalities being the most common (hypokinesia,
akinesia and/or dyskinesia).18
Non-specific markers of inflammation, erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP) Figure-2: Histopathological findings in myocarditis in children (A, B) acute myocarditis
have been found to be elevated in 27-56% of cases of (C, D) chronic myocarditis. In acute myocarditis, numerous necrotic myocytes (A,
paediatric myocarditis.7 Troponin I and troponin T are arrows) are associated with mononuclear cell infiltrates including CD3+ T cells (B),
cardio-selective markers released in the blood stream, whereas in chronic myocarditis, inflammatory cells such as CD68+ macrophages (D) are
hours following cardiac insult. Cardiac troponin T (cTnT) mainly present in areas with fibrosis (C, blue staining). (E, F) Radioactive in situ
has been found to be elevated in children with hybridization reveals PVB19 nucleic acid in endothelial cells of an arteriole in a patient
myocarditis.21 Levels> 0.052 mg/ml have a sensitivity of with chronic myocarditis (E), whereas enterovirus ribonucleic acid is detected in several
71% and specificity of 86% for paediatric myocarditis.21 myocytes (F). Adapted from Kindermann I et al.5
Recently, aspartate aminotransferase (AST) was also
studied and was found to be a highly sensitive marker for complications in paediatric population, including
diagnosis of paediatric myocarditis as it was seen to be pneumothorax, haemothorax, dysrhythmia, heart block,
elevated in 85% cases of definite and probable cases of myocardial perforation and death.23 Moreover, EMB, when
myocarditis. However, AST levels are non-specific and may used alone, is not sensitive owing to patchy nature of
be raised in conditions such as Kawasaki syndrome, myocardial inflammation.3
hypoperfusion and other viral illnesses.23
Cardiac magnetic resonance imaging (CMRI) has recently
Soongswang et al21
further assessed the use of serum evolved as a non-invasive and valuable diagnostic
cTnT and creatinine kinase-muscle and brain levels as modality for myocarditis. CMR, with early and delayed
non-invasive indicators to differentiate acute myocarditis gadolinium enhancement, can often detect the subtle
and chronic DCM in paediatric patients. The two levels patchy myocardial involvement and can demarcate areas
were shown to be significantly higher in patients with of inflammation.22 Thus, CMR can help not only in
myocarditis than in patients with DCM.21 diagnosing myocarditis, but can guide EMB procedure.
Vashist at el7 in his retrospective study concluded that
EMB still remains the gold standard for diagnosis of myocarditis in children is characterised by sub-pericardial
myocarditis. Specific histopathological features found on and transmural enhancement. Transmural myocardial
microscopic examination of the biopsy specimen in a involvement, global hypokinesia, LV dilation, and LV
myocarditis patient are shown in Figure-2A-F. Polymerase ejection fraction less than 30% were shown to be
chain reaction (PCR) performed on the myocardial tissue associated with poor prognosis.
has proved to be both sensitive and specific in diagnosing
entero- and adenoviral myocarditis. However, EMB is an Treatment
invasive procedure and can lead to dangerous The mainstay of treatment in paediatric myocarditis

J Pak Med Assoc

Management of acute myocarditis in children 807

Figure-3: Management of myocarditis in emergency department; endomyocardial biopsy and cardiac magnetic resonance imaging not mentioned as not readily available in resource-
limited developing world.

Vol. 63, No. 6, June 2013

808 Q. Merchant, A. Haque, B. S. Hasan

(PPV: Positive pressure ventilation. CVS: Cardiovascular system.

CVL: Central venous line. CNS: Central nervous system.)

Figure-4: Paediatric intensive care unit and ward management of myocarditis.

J Pak Med Assoc

Management of acute myocarditis in children 809

remains supportive symptom-based care (Figure-3). Most especially carvedilol, are well known to improve survival
of the children will recover fully without any long-term in adult patients with CHF, a 2009 Cochrane review on
sequelae.4 General principles of supportive treatment in efficacy of beta blockers in children with CHF failed to
acute phase include reduction of high ventricular preload, demonstrate statistically significant benefit of beta
reduction of ventricular afterload, improving myocardial blockers.24,25 Moreover, a recent randomised control trial
contractility and optimisation of tissue oxygen delivery carried out by Shaddy et al25 failed to show any significant
(Figure-4).2 benefit of carvedilol in children with heart failure.
However, the study suggested, this can be secondary to
Symptom-based Care Therapy parents and physician's false perception of normal
Children presenting with signs and symptoms of CHF developmental milestones (starting to walk) as indicators
should be aggressively managed with administration of of cardiovascular status.25
inotropic support, afterload reduction and diuresis. In
acute or decompensated heart failure, diuretics are L-carnitine is employed in treatment of myocarditis as it is
frequently administered as removal of excess fluid from known to prevent apoptosis of muscle cells and plays a
the body helps to improve cardiac function.9 However, role in CHF associated myopathies.
diuretics should be administered with care as too rapid a
Rhythm disturbances in children with myocarditis are life-
removal of fluid may lead to hypovolaemia and
threatening and should be aggressively treated.
hypotension.9 Fluid resuscitation should also be done
Ventricular ectopy, ventricular tachycardia and heart
with caution, especially in undiagnosed myocarditis
block may develop in children with myocarditis. Digoxin
patients presenting as septic shock where aggressive fluid
resuscitation may be detrimental. should be used with extreme care during the acute phase
of the disease as high doses lead to increased production
For more severe disease, an inotropic agent, such as of pro-inflammatory cytokines and can precipitate serious
dobutamine or dopamine, can be added, especially if dysrhythmias. However, its use is still questionable in
cardiac output is inadequate and cardiac function is cases of DCM and chronic heart failure.2,17
depressed on ECG. They should be administered with
caution due to risk of arrhythmias. Dobutamine improves Positive pressure ventilation (PPV) can be employed in
contractility and decreases afterload, while dopamine has cases of ventricular dysfunction as it can eliminate work of
both inotropic and vasopressor properties and is useful in breathing, and can lead to decrease in LV wall tension and,
patients with cardiogenic shock with hypotension.17 thus, afterload reduction. In case of failure of medical
Severe shock may require the addition of epinephrine as treatment, mechanical assistance devices with ECMO, and
well. Moreover, milrinone, a phosphodiesterase inhibitor, transthoracic placement of a left or biventricular assist
can also be administered as it helps improve the diastolic device (LVAD/BVAD) may also be used given the overall
function of the heart and, hence, improve ventricular prognosis for recovery. However, cardiac transplantation
relaxation and filling times. Milrinone is considered is the last resort in cases of end-stage DCM.
inotropic agent of choice at many centres owing to its
Mechanism Specific Interventions
positive effect on the cardiac index, reduction in systemic
Many studies have been done to evaluate the efficacy of
vascular resistance and comparatively less side effects in
adjuvant therapeutic interventions, specifically
terms of arrhythmogenic properties.17
intravenous immunoglobulins (IVIG) to reduce long-term
Use of beta blockers in the treatment of myocarditis in cardiac complications. While some of the studies both in
children remains controversial. Although beta blockers, developing26 and the developed world have

Vol. 63, No. 6, June 2013

810 Q. Merchant, A. Haque, B. S. Hasan

demonstrated statistically significant increase in survival Conclusion

among those children treated with IVIG,27 a recently Myocarditis is a challenging diagnosis to make on
conducted multi-institutional analysis on outcome of clinical grounds owing to the wide array of clinical
paediatric myocarditis failed to show any survival benefits presentation, and requires high index of suspicion.
of using IVIG.28 Generally, medical practitioners become suspicious of
Apart from immunoglobulin, immunosuppressive myocarditis when there is tachycardia in an otherwise
therapies are also possible adjuvant to therapeutic healthy child without a clearly defined cause. The main
modalities in the treatment of myocarditis. Before cornerstone of treatment remains supportive although
initiating immunoglobulin therapy, EMB with PCR therapeutic modalities such as immunosuppressive
should be done to rule out any viral load as therapy and IVIGs are being extensively studied. With
immunomodulator use in myocarditis with concomitant the advent of newer diagnostic and therapeutic
viral load may lead to detrimental effect.29 The sole modalities and improved therapy for heart failure,
randomised control trial performed by Camargo et al30 including mechanical cardiovascular support, the
randomised paediatric patients with biopsy-proven viral overall prognosis of the disease is getting better with
myocarditis into three groups: prednisone only; or 80% survival rates.
prednisone and azathioprine; or prednisone, References
azathioprine and cyclosporine. The study concluded that 1. Batra AS, Lewis AB. Acute myocarditis. Curr Opin in Pediatr 2001;
combination immunosuppressive therapy leads to 13: 234-9.
improvement in cardiac outcome. 30 Aziz et al 29 2. Dancea AB. Myocarditis in infants and children: a review for the
researched the role of prednisone at 3 months of onset paediatrician. Paediatr Child Health 2001; 6: 543-5.
3. Sparrow PJ, Merchant N, Provost YL, Doyle DJ, Nguyen ET, Paul NS.
of viral myocarditis and concluded that it is beneficial CT and MR imaging findings in patients with acquired heart
and causes significant improvement in persistent LVF.29 disease at risk for sudden cardiac death. Radiographics 2009; 29:
Another meta-analysis done by Hia et al31 to assess the 805-23.
benefits of immunosuppressive therapy in the 4. Amabile N, Fraisse A, Bouvenot J, Chetaille P, Ovaert C. Outcome of
acute fulminant myocarditis in children. Heart 2006; 92: 1269-73.
management of viral myocarditis showed that the odds 5. Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, et
of improved outcome were more among patients al. Update on myocarditis. J Am Coll Cardiol 2012; 59: 779-92.
treated with immunosuppressive therapy. However, the 6. Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett
results were not statistically significant.31 The current D, et al. Contemporary definitions and classification of the
cardiomyopathies. Circulation. 2006; 113: 1807-16.
prevailing consensus regarding immunosuppressive 7. Vashist S, Singh GK. Acute myocarditis in children: current
therapy is that it does impart a survival advantage, concepts and management. Curr Treat Options Cardiovasc Med
although there is need of further evaluation.31 2009; 11: 383-91.
8. Feldman AM, McNamara D. Myocarditis. N Engl J Med 2000; 343:
Prognosis and Outcome 1388-98.
9. Tobias JD, Deshpande JK, Johns JA, Nichols DG. Inflammatory
Even though true incidence of myocarditis in children heart disease. In: Nichols DG, Cameron DE, eds. Critical Heart
cannot be known owing to sub-clinical presentations, Disease in Infants and Children. Philadelphia, PA: Mosby, 2006; pp
some studies estimate it to be around 1 per 100,000.32 The 899-925.
incidence of myocarditis in developing countries is seen 10. Kindermann I, Kindermann M, Kandolf R, Klingel K, Bültmann B,
Müller T, et al. Predictors of outcome in patients with suspected
more in the winter months owing to increase in upper myocarditis. Circulation 2008; 118: 639-48.
respiratory tract infections (URIs).33 The survival rate is 11. Cooper Jr LT. Myocarditis. N Engl J Med 2009; 360: 1526-38.
more than 80% in the first year, but 25%-50% of the cases 12. Kearney MT, Cotton JM, Richardson PJ, Shah AM. Viral myocarditis
may develop DCM and chronic heart failure.2,34 Out of and dilated cardiomyopathy: mechanisms, manifestations, and
management. Postgrad Med J 2001; 77: 410.
children who develop DCM, the 1-year and 5-year rates of 13. Matsumori A. Molecular and immune mechanisms in the
death and heart transplantation are 31% and 46% pathogenesis of cardiomyopathy: role of viruses, cytokines and
respectively. It has also been seen that the patients who nitric oxide. Jpn Circ J 1997; 61: 275-91.
survive the first 72 hours without requiring ECMO have a 14. Leonard EG. Viral myocarditis. Pediatr Infect Dis J 2004; 23: 665-6.
15. McCarthy RE, Boehmer JP, Hruban RH, Hutchins GM, Kasper EK,
survival rate of 97%. Viral persistence in the myocardium,
Hare JM, et al. Long-term outcome of fulminant myocarditis as
ejection fraction less than 30% and moderate to severe compared with acute (nonfulminant) myocarditis. N Engl J Med
mitral regurgitation have been associated with adverse 2000; 342: 690-5.
outcome.35 Hence, early administration of IVIGs may help 16. D'Ambrosio A, Patti G, Manzoli A, Sinagra G, di Lenarda A, Silvestri
F, et al. The fate of acute myocarditis between spontaneous
in the reduction of long-term complications by
improvement and evolution to dilated cardiomyopathy: a review.
decreasing the viral load. However, further studies are Heart 2001; 85: 499-505.
required to evaluate its role. 17. Gupta D, Garg G, Tomar CRPS. Myocarditis in Children. The

J Pak Med Assoc

Management of acute myocarditis in children 811
Intensivist: Newsletter of Intensive Care Chapter, Indian Academy 26. Haque A, Bhatti S, Siddiqui FJ. Intravenous immune globulin for
of Pediatrics. January 2009. severe acute myocarditis in children. Indian Pediatr 2009; 46: 810-1.
18. Durani Y, Egan M, Baffa J, Selbst SM, Nager AL. Paediatric 27. Camargo PR, Okay TS, Yamamoto L, Del Negro GM, Lopes AA.
myocarditis: presenting clinical characteristics. Am J Emerg Med Myocarditis in children and detection of viruses in myocardial
2009; 27: 942-7. tissue: implications for immunosuppressive therapy. Int J Cardiol
19. Morgera T, Di Lenarda A, Dreas L, Pinamonti B, Humar F, Bussani R, 2011; 148: 204-8.
et al. Electrocardiography of myocarditis revisited: clinical and 28. Klugman D, Berger JT, Sable CA, He J, Khandelwal SG, Slonim AD.
prognostic significance of electrocardiographic changes. Am Pediatric patients hospitalized with myocarditis: a multi-
Heart J 1992; 124: 455-67. institutional analysis. Pediatr Cardiol 2010; 31: 222-8.
20. Freedman SB, Haladyn JK, Floh A, Kirsh JA, Taylor G, Thull- 29. Aziz KU, Patel N, Sadullah T, Tasneem H, Thawerani H, Talpur S.
Freedman J. Paediatric myocarditis: emergency department Acute viral myocarditis: role of immunosuppression: a prospective
clinical findings and diagnostic evaluation Pediatrics 2007; 120: randomised study. Cardiol Young 2010; 20: 509-15.
1278-85. 30. Camargo PR, Snitcowsky R, da Luz PL, Mazzieri R, Higuchi ML, Rati
21. Soongswang J, Durongpisitkul K, Ratanarapee S, Leowattana W, M, et al. Favorable effects of immunosuppressive therapy in
Nana A, Laohaprasitiporn D, et al. Cardiac troponin T: its role in the children with dilated cardiomyopathy and active myocarditis.
diagnosis of clinically suspected acute myocarditis and chronic Pediatr Cardiol 1995; 16: 61-8.
dilated cardiomyopathy in children. Pediatr Cardiol 2002; 23: 531-5. 31. Hia CPP, Yip WC, Tai BC, Quek SC. Immunosuppressive therapy in
22. Cowley CG, Lozier JS, Orsmond GS, Shaddy RE. Safety of acute myocarditis: an 18 year systematic review. Arch Dis Child
endomyocardial biopsy in children. Cardiol Young 2003; 13: 404-7. 2004; 89: 580-4.
23. Goitein O, Matetzky S, Beinart R, Di Segni E, Hod H, Bentancur A, et 32. Stiller B. Management of myocarditis in children: the current
al. Acute myocarditis: noninvasive evaluation with cardiac MRI situation. Adv Exp Med Biol 2008; 609: 196-215.
and transthoracic echocardiography. AJR Am Roentgenol 2009; 33. Aziz KU. Acute myocarditis in children, incidence, treatment and
192: 254-8. prognosis: a developing world problem. Pak Paed Cardiolo J 2001;
24. Frobel AK, Hulpke-Wette M, Schmidt KG, Läer S. Beta-blockers for 3: 24-9.
congestive heart failure in children. Cochrane Database Syst Rev 34. Bruns LA, Chrisant MK, Lamour JM, Shaddy RE, Pahl E, Blume ED, et
2009; CD007037. al. Carvedilol as therapy in pediatric heart failure: an initial
25. Shaddy RE, Boucek MM, Hsu DT, Boucek RJ, Canter CE, Mahony L, multicenter experience. J Pediatr 2001; 138: 505-11.
et al. Carvedilol for children and adolescents with heart failure: a 35. Kühn B, Shapiro ED, Walls TA, Friedman AH. Predictors of outcome
randomized controlled trial. JAMA 2007; 298: 1171-9. of myocarditis. Pediatr Cardiol 2004; 25: 379-84.

Vol. 63, No. 6, June 2013