This document discusses myocarditis in children. It defines myocarditis and describes the epidemiology, etiology, pathophysiology, clinical presentation, diagnosis and treatment. Myocarditis has many potential causes including viruses like adenovirus and enterovirus. Clinically it presents variably depending on age from nonspecific symptoms to heart failure. Diagnosis involves blood tests, ECG, imaging like echocardiogram and cardiac MRI, and endomyocardial biopsy. Treatment is supportive with heart failure medications, antivirals may help, and immunosuppressants can reduce inflammation and improve function.

1. MYOCARDITIS IN CHILDREN
Dr. Pradeep Singh

2. TO BE COVER…..
• DEFINITION
• EPIDEMIOLOGY AND ETIOLOGY
• PATHOPHYSIOLOGY
• CLINICAL PRESENTATION
• DIFFERENTIAL DIAGNOSIS
• DIAGNOSIS
• TREATMENT
• PROGNOSIS

3. definition
• Acute myocarditis -inflammation, necrosis, or
myocytolysis and caused by many infectious, conn.
tissue, granulomatous, toxic, or idiopathic processes
affecting the myocardium with or without associated
systemic manifest of the disease process or
involvement of the endocardium or pericardium
Nelson Textbook of Pediatrics, 18th ed.
• Acute fulm myocarditis - myocellular necrosis, lead
to sudden onset of heart failure, arrhythmia and
sudden death

4. Epidemiology
•True incidence is difficult to determine
•Incidence of biopsy documented myocarditis in
patients with unexplained heart failure is 9.6%.
Progress in Cardiovascular Diseases 52 (2010) 274–288
• 29 children with DCM
-38% have histopatho evidence of ‘definite’ or
-borderline’ myocarditis accord to the Dallas criteria.
Cardiac symposium on Viral myocarditis in childhood:Juan Pablo Kaski ,
Michael Burch

5. ETIOLOGY

7. Adenovirus - common cause of myocarditis
• 624 patients with
-biopsy-proven myocarditis (66%)
-borderline myocarditis (34%).
- viral genome of adenovirus
-enterovirus
-cmv in dec freq
• detected in 239 (38%)
Bowles NE, et al Detection of viruses in myocardial tissues by PCR:
J Am Coll Cardiol. 2003;42:466–472.

8. DENGUE VIRUS – CAUSE OF MYOCARDITIS
• DHF/DSS- poor LVEF
• Worsened by the hypotension and shock
• Sinus node dysfunction reported
Wali JP, Biswas A, Chandra S, Malhotra A, Aggarwal P, Handa R, et al.
Cardiac involvement in dengue haemorrhagic fever. Int J Cardiol
1998;64:31-

9. RISK FACTORS
• Increased risk of virus-induced myocarditis
• The course is hyperacute
– Young males
– pregnant women
– children ( neonates)
– immunocompromised patients
– selenium deficiency
-vitamin E deficiency
Beck MA, Levander OA, Handy J: Selenium deficiency and viral
infection. J Nutr 2003;133(5 Suppl 1):1463-1467

10. PATHOPHYSIOLOGY

12. Toxins & hypersensitivity reactions
• Direct toxic effect on the heart
or
by hypersensitivity reactions
•Hypersensitivity reactions – eosinophilic myocarditis
•Responds to withdrawal of the offending medication

13. myocardial injury
cardiac enlargement and an inc. in the vent end-diastolic
volu.
myocardium is unable to respond to these stimuli
reduced cardiac output
Moss and Adams' Heart Disease in Infants, Children, and Adolescents:
Including the Fetus and Young Adults, 7th Edition

14. Preserve systemic blood flow via vasoconstriction
& elevated afterload.
intact sympathetic nervous system input
tachycardia and diaphoresis,CHF
prog ventricular end-diastolic volu
left atrial pres
pulmonary edema.

15. Concomitantly
All cardiac chambers dilate(LV)
Dilation causes poor ventricular function
Worsening pulmonary edema & cardiac function.
Stretching of the mitral annulus & mitral regurg
Further increasing left atrial volume & pressure
Moss and Adams' Heart Disease in Infants, Children, and Adolescents:
Including the Fetus and Young Adults, 7th Edition

16. Clinical features
• Presentation in children varies according to
age.
• Lesser the age ,poor prognosis
• Newborns or infants- poor appetite, fever,
irritability or listlessness
• Pallor and diaphoresis,Sudden death
• Mild cyanosis to sympts of CHF

17. Children and Adolescents
• Recent history of viral disease 10 to 14 days prior
to presentation
•Lethargy, low-grade fever, pallor decreased appetite
• Diaphoresis, palpitations, rashes, exercise
intolerance
•Raised JVP,Rales,with resting techycardia
• Respiratory symptoms become predominant; syncope
or sudden death
Moss and Adams' Heart Disease in Infants, Children, and Adolescents:
Including the Fetus and Young Adults, 7th Edition

18. • Presentation at the emerg. department
-Respiratory distress (68%);
-Tachycardia (58%)
- Lethargy (39%)
-Hepatomegaly (36%)
-Abnormal heart sounds, murmur (32%);
-Fever (30%)
Progress in Cardiovascular Diseases 52 (2010) 274–288 Lori A.
Blauwet, Leslie T. Cooper†
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN

19. DIFFERENTIAL
DIAGNOSIS

20. Newborn and Infant Child
• Sepsis
• Hypoxia
• Hypoglycemia
• Hypocalcemia
• Idiopathic dialated
cardiomyopathy
• Endocardial
fibroelastosis
• Anomalous left coronary
artery from Pulm artery
• Idiopathic dilated
cardiomyopathy
• X-linked dilated
cardiomyopathy
• Autosomal dominant dilated
cardiomyopathy
• Endocardial fibroelastosis
• Chronic tachyarrhythmia
• Pericarditis
• Cerebral arteriovenous
malformation

21. Laboratory
• CBC, Blood c/s
• E.S.R, C-reactive protein and leukocyte count are
elevated BUT nonspecific
• (TnI) or troponin T (TnT) are more common than
inc.CPK-MB with acute myocarditis
• In children, TnT have a specificity of 83% and a
sensitivity of 71%
• Higher levels of TnT poor prognostic marker
• Viral serology n viral PCR Myocarditis
Lori A. Blauwet, Leslie T. Cooper† Division of Cardiovascular
Diseases, Mayo Clinic, Rochester, MN

22. VIRAL GENOMES IN TRACHEAL SECRETION
DISEASE NO. OF
SAMPLES
NO. OF
POSITIVE
PCR SAMPLES
NO. OF PCR
AMPLIMERS
MYOCARDITIS 624 239(38%) Adenovirus 142
(23%)
Enterovirus 85 (14%)
CMV 18 (3%)
Parvovirus 6 (<1%)
Influenza A 5 (<1%)
HSV 5 (<1%)
EBV 3 (<1%)
DCM 149 30(20%) RASdeVn 1o v(<ir1u%s) 18 (12%)
Enterovirus 12 (8%
CONTROLS 215 3(1.4%) Enterovirus 1 (<1%)
CMV 2 (<1%)
Moss and Adams' Heart Disease in Infants, Children, and Adolescents:
Including the Fetus and Young Adults, 7th Edition

23. newer markers
 serum Fas and Fas ligand on initial presentation
asso.with increased mortality
 IL-10 has a poor prognosis in fulminant
myocarditis
Progress in Cardiovascular Diseases 52 (2010) 274–288 .Myocarditis,Lori A.
Blauwet, Leslie T. Cooper†
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN

24. Electrocardiogram
• Sensitivity is only 47%
• Findings are nonspecific
- PR depression,
-Pathologic Q waves.
-ST-segment elevation/ depression
-T-wave changes
• Low QRS voltages (< 5mm in any precordial lead)
• New-onset supraventricular or ventricular
arrhythmias in up to 55%

25. Chest x-ray
• Cardiomegaly due to chamber dilatation,
pericardial effusion or both.
• Pulmonary venous congestion, interstitial
infiltrates
• Pleural effusions.

27. Echocardiography
• Chamber size, wall thickness,systolic diastolic
functions & intracavitary thrombi
• Rule out other causes of heart failure
• LV systolic dysfunction is common
• Rt ventricular dysfunction is relatively uncommon
• Rt vent dysfunction most powerful predictor of
death or need for cardiac transplantation in a
series of 23 patients with biopsy-confirmed
myocarditis
Mendes LA, Dec GW, Picard MH, et al: Right ventricular dysfunction: an
independent predictor of adverse outcome inpatients with
myocarditis. Am Heart J 1994;128:301-307.

28. • Segmental or global wall motion abnormalities
• Diastolic filling patterns are abnormal
Moss and Adams' Heart Disease in Infants, Children, and
Adolescents: Including the Fetus and Young Adults, 7th Edition

29. Cardiac MRI
• Intracellular and interstitial edema,hyperemia and
capillary leakage,necrosis and fibrosis
• symptomatic patients with clinical suspicion of
myocarditis
• Diagnostic accuracy of 78%

30. Proposed cardiac MRI diagnostic criteria for
myocarditis(Lake Louise Criteria )
A. In clinically suspected myocarditis-consistent with
myocardial inflammation if at least 2 of the following criteria
are present:
1.Regional or global myocardial signal intensity increase in T2-
weighted images
2. Increased global myocardial early enhancement ratio
between myocardium and skeletal muscle in gadolinium-enhanced
T1-weighted images
3. There is at least 1 focal lesion with non ischemic regional
distribution in inversion recovery-prepared gadolinium-enhanced
T1-weighted images (delayed enhancement)
Progress in Cardiovascular Diseases 52 (2010) 274–288 .Myocarditis,Lori A.
Blauwet, Leslie T. Cooper†

31. Lake Louise Criteria contd..
• B. Cardiac MRI study is consistent with myocyte
injury and/or scar caused by myocardial
inflammation if criterion 3 is present
• C. A repeat cardiac MRI study between 1 to 2
weeks after the initial,cardiac MRI study is
recommended if
• None of the criteria are present, but onset of
symptoms is very recent and there is strong
clinical evidence for myocardial inflammation
One of the criteria is present
• D. The presence of LV dysfunction or pericardial
effusion provides additional supportive evidence
for myocarditis

32. Endomyocardial biopsy
• Recommended in---
1. Fulminant myocarditis- unexplained new-onset CHF
symptoms < 2 weeks in duration a/w
- normal sized or dilated left ventricle
-hemodynamic compromise
2.Unexplained new onset CHF symptoms 2 weeks to 3
months in duration a/w with a
-dilated left ventricle
-new ventricular arrhythmias,
-high-degree AV heart block, or
-failure to respond to usual care within 1 to 2
weeks

33. The Dallas criteria(1986)- based on the presence of histological
evidence
Four types of myocarditis are recognised:
Active myocarditis- the presence of both myocyte degeneration
or necrosis and definite cellular infiltrate, with
or without fibrosis;
Borderline myocarditis-when there is a definite cellular
infiltrate but no evidence of myocyte injury;
Persistent myocarditis- continued active myocarditis
on repeat EMB;
Resolving/resolved myocarditis, determined by diminished or
absent infiltrate with evidence of connective tissue healing

34. LIMITATIONS OF DALLAS CRITERIA
• Lack of prognostic value
• Discrepancy with other markers of
viral infection and immune activation in
the myocardium,
• Low sensitivity that is at least partly
due to sampling error

35. World Health Organization
(Marburg) Classification
Cooper LT Jr. Myocarditis. N Engl J Med. 2009
Apr 9;360(15):1526-38.

36. First biopsy:
•Acute (active) myocarditis: a clear-cut infiltrate (diffuse, focal
or confluent) of >14 leukocytes/mm Infiltrate quantified by
immunohistochemistry. Necrosis or degeneration is compulsory;
• fibrosis- absent or present and should be graded.
•Chronic myocarditis: Infiltrate of >14 leukocytes/mm2 (diffuse,
focal or confluent), Quantified by immunohistochemistry.
Necrosis or degeneration not + usually.
•No myocarditis: No infiltrating cells or <14 leukocytes/mm2.

37. Subsequent biopsies:
•Ongoing (persistent) myocarditis. Criteria as in acute
or chronic myocarditis
•Resolving (healing) myocarditis. Criteria as in acute
or chronic myocarditis, but the immunologic process
is sparser than in the first biopsy.
•Resolved (healed) myocarditis. Corresponds to the
Dallas classification

38. Expanded criteria for diagnosis of myocarditis
•Suspected= 2 positive categories
•Compatible = 3 positive categories
•High probability = all 4 categories positive.
NOTE: Any matching feature in category = positive for category
Category I: symptoms:
•Clinical heart failure
•Fever
•Viral prodrome
•Fatigue
•Dyspnoea on exertion
•Chest pain
•Palpitations
•Pre-syncope or syncope

39. Category II: evidence of cardiac
structural/functional perturbation in the absence of
regional coronary ischaemia
•Echo evidence
•Regional wall motion abnormalities
•Cardiac dilation
•Regional cardiac hypertrophy
•Troponin release
•Troponin result has high sensitivity (>0.1
nanogram/mL)
•+ve indium-111 antimyosin scintigraphy and normal
coronary angiography or
-sence of reversible ischaemia on perfusion
scan

40. Category III: cardiac MRI
•Increased myocardial T2 signal on inversion
recovery sequence
•Delayed contrast enhancement following
gadolinium- DTPA infusion.
Category IV: myocardial biopsy, pathologic or
molecular analysis
•Pathology findings compatible with Dallas
criteria
•Presence of viral genome by PCR or in situ
hybridisation.

41. Treatment

42. •Stabilze the patient- ABC
•Any previously well child with a viral prodrome and non-specific
organ dysfunction
• A/w dysrhythmias, shock or acute heart failure
•Even in the absence of cardiomegaly
Early mechanical support can be very favourable
•Delay in diagnosis may result in poor outcome.
The Challenges of Prompt Identification and Resuscitation in Children with
Acute Fulminant Myocarditis: Geethanjali Ramachandra; Lynn Shields et al
Journal of Paediatrics and Child Health Vol: 46, No: 10, October, 2010

43. Heart failure therapy
• Ac. myocarditis - standard heart failure therapy
- diuretics-furosemide
-ACE Inhibitor -captopril (1 to 3 mg/kg/dX8hrly )
enalapril (0.2 mg/kg/d x 12h)
• Introduction of β-blockers such as bisoprolol,
metoprolol or carvedilol in clinically stable
• Digoxin should be used with caution and only in low
doses in patients with viral myocarditis
Braunwald's Heart Disease: A Textbook of Cardiovascular
Medicine, 8th ed.

44. Antiviral therapy
• Data in humanbeing not available
• In the single case series of antiviral therapy use in
humans with fulminant myocarditis, ribavirin therapy
did not prove effective
• T/t with interferon b resulted in the elimination of
the viral genomes and improved LVEF is in trials
Kuhl U, Pauschinger M, Schwimmbeck PL, et al. Interferon- b treatment
eliminates cardiotropic viruses and improves LVF in patients with
myocardial persistence of viral genomes and left ventricular dysfunction.
Circulation 2003;107:2793

45. Immunosuppressive therapy
• Prednisone (2 mg/kg daily, tapered to 0.3 mg/kg
daily over a period of 3 mo)
• Reduce myocardial inflammation and improvedcardiac
function.
• Relapse -in some patient on discontinuation
• Beneficial in treating patients with chronic DCM
unresponsive to standard heart failure therapy.
Nelson Textbook of Pediatrics, 18th ed.

46. • Prednisolone given 3-month duration
•44 prednisolone group & control group of
24children.
•Prednisolone-treated group increased EF > 40%
• Prednisolone improved EF and cure in persistent
LVF
Acute Viral Myocarditis: Role of Immunosuppression: A Prospective
Randomised Study Kalim U. Aziz; Najma Patel; et al Cardiology in the
Young Vol: 20, No: 5, October, 8 2010

47. Role of iv Ig
•No randomized controlled trials in children
•Case series shown that use of high-dose IVIG
improved recovery of left ventricular function and
better survival.
• Routine use of IVIG is not recommended in adults
•Consider in acute myocarditis in children

48. Intravenous Ig for Severe Acute Myocarditis in
Children
• high-dose (2g/kg) IVIG in 13 children
•12 children treated with only conventional therapy.
•Both groups had poor LVEF on admission.
The mortality rate was 8% in the IVIG treated
children as compared to 46% in controls.
Anwarul Haque, Samreen Bhatti et al, Indian paediatrics,volume
46,september17, 2009

49.  report two children with fulminant myocarditis
successfully treated with a 10-h infusion of high-dose
IVIG.

50. I.V Ig inT/t of Acute Myocarditis in the
Pediatric Population
•IVIG is a/w improved recovery of left vent.
function
•Better survival during the first year
Nancy A. Drucker, MD; Steven D. Colan, MD;
(Circulation. 1994;89:252-257.)

51. •Patients with recent-onset DCM IVIG does not
augment the improvement in LVEF .
• LVEF improved significantly during follow-up.
Controlled Trial of Intravenous Immune Globulin in recent-
Onset Dilated Cardiomyopathy. Dennis M. McNamara, MD;
Richard Holubkov, PhD; Randall C. Starling, MD; G. William
Dec, MD Circulation. 2001;103:2254-2259.)

52. •Lupus Myocarditis: Marked Improvement in Cardiac
Function after IVIg Therapy
• 18-year-old man of active lupus with worse cardiac systolic
function who did not respond to pulse
methylprednisolone and cyclophosphamide,
•Improved cardiac function after IVIg
• IVIg -dermatomyositis/polymyositis, Kawasaki dis, and viral
myocarditis
Vikas Suri; S.Verma; Sanjay Jain etal PGIMER chandigarh
Rheumatology International Vol: 30, No:11, September, 2010

53. Ant arrhythmic treatment
•AV block & tachyarrhythmias treated with approp.
medications
• Placement of a temporary or permanent pacemaker
•Arrhythmias resolve after several weeks.
• Symptomatic or sustained vent tachycardia require
antiarrhythmic therapy or
• Implantable cardioverter-defibrillator or cardiac
transplantation if arrhythmias persist after the
acute inflammatory phase.

54. Patient with myocarditis
Stablize
with
diuretics/vas
odilator
Inotrope/balloon
pump/VAD
Remodelling
therapy(ACE/ARB-,
BETA BLOCKER
Immune Rx, consider bx,
Steroids/azathiopri/IFs
F/U repeat echo
If LVEF <35%-
CONSIDER AICD
Cardiac transplantation
Mechanical assist
unstable
stable
stable
unstable
unstable
unstable
stable

55. FUTURE TRENDS
•Sophora flavescens (SF) - viral hepatitis, cancer, viral
myocarditis, gastrointestinal hemorrhage, and skin disease
•SF up-regulates CYP3A expression.
• Cetirizine- beneficial in viral myocarditis by suppressing
expression of pro-inflammatory cytokines
•Antiviral Effect of Bosentan and Valsartan during
Coxsackievirus B3 Infection of Human Endothelial Cells
•CAR-downregulation in human umbilical vein endothelial cells
(HUVEC) & helpful in viral myocarditis
•Cinnamaldehyde has antiviral effects on VMC &
directly reduces the inflammation by inhibiting the
TLR4

56. Physical activity
• Withdraw from competitive sports & vigorous
exercise >6months or longer
OR
• Recovery of left ventricular function.
Moss and Adams' Heart Disease in Infants, Children, and
Adolescents: Including the Fetus and Young Adults, 7th Edition

57. Prognosis
• fulm myocarditis-excellent long-term prognosis
complete recovery of LVF than patients with acute
myocardit- after acute phase over
• 70 children with acute myocarditis
- 73%had histologic resolution of myocarditis at 6
month
- 96% survived to 1 year
Moss and Adams' Heart Disease in Infants, Children, and Adolescents: Including
the Fetus and Young Adults, 7th Edition

58. Outcome of acute fulminant myocarditis in children
•Diagnostic criteria- +sence of severe and acute heart failure;
-LV dysfunction on echo
- recent history of viral illness
-no history of cardiomyopathy.
•Results: 11 pt from 1998 to 2003, median age 0 to 9 yr.
•LVEF was 22 at presentation
• Inotropic support required in 9 pt & 8 ventilated.
• All patients received corticosteroid, IVIg in seven.
•5 pt had arrest & revived in four.
•F/U of 58.7 (33.8–83.1) months
• 10 survivors are asymptomatic with normal LVEF
Heart 2006;92:1269-1273

59. Prognosis…..
With severe left ventricular dysfunction
-25% progress to transplantation
-50% develop chronic DCM
- 25% recover spontaneously
• 41 children with acute myocarditis treated with
immunosuppressive Rx,
• At 5 years, 3/4 th patients had complete recovery
• 1/4th died or required cardiac transplantation
Gagliardi MG, Bevilacqua M, Bassano C, et al: Long term followup of children with
myocarditis treated by immunosuppression and of children with dilated
cardiomyopathy. Heart (British CardiacSociety) 2004;90:1167-1171.

60. THANKS

61. Taylor and Jennifer J. Kimberly Haladyn, Alejandro Floh, Joel A. Kirsh, Glenn
Pediatrics 2007;120;1278-1285
,

62. MOST COMMON
• Viral- Adenovirus 9% to 39% of cases.
• Enterovirus 71 (coxsackie B) hepatitis C
virus,herpes viruses (HHV-6) HIV,Parvovirus B 19
• BACTERIAL-Coryne. Diphtheriae, Mycobac.
tuberculosis Strept A,Strept. pneumoniae
• Spirochetal: Borrelia burgdorferi
• Hypoxia, hypothermia in neonates
Moss and Adams' Heart Disease in Infants, Children, and Adolescents:
Including the Fetus and Young Adults, 7th Edition

64. Progress in Cardiovascular Diseases 52 (2010) 274–288 .Myocarditis,Lori A.
Blauwet, Leslie T. Cooper†
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN