This document summarizes the management of myocarditis. It discusses the diagnosis of myocarditis through lab evaluation including troponins, natriuretic peptides and endomyocardial biopsy. It outlines the treatment of myocarditis including activity restrictions, medical management with immunosuppressors, antivirals and mechanical circulatory supports. It also discusses survival and the potential need for heart transplantation in severe cases.

1. MANAGEMENT OF
MYOCARDITIS
Murtaza Kamal
26/03/2019

2. SCOPE OF THE TALK: MINI SEMINAR
Diagnosis:
Lab evaluation
ECX/ CXR/ ECHO
CMR
EMB
Treatment:
Activity restrictions
Medical management
Immunomodulators, Immunosuppressors
Antivirals
Mechanical circulatory supports
Survival and heart transplantation
2

3. 3

4. WHO DEFINITION
An inflammatory myocardial disease diagnosed by a combination
of histologic, immunologic, and immunohistochemical criteria
Richardson P, McKenna W, Bristow M, et al. Report of the 1995 World Health Organization/International Society and Federation of
Cardiology Task Force on the Definition and Classification of cardiomyopathies. Circulation. 1996;93(5):841–842
4

5. CLINICAL PRESENTATION+ PHYSICAL
EXAMINATION
HF symptoms of short duration—> Days to weeks
H/o recent viral prodrome with fever: RTI/ GIT
RTI: 80%
Vitals: Tachycardia/ Tachypnea/ Hypotention/ Hypoperfusion
Lethargy/ Hepatomegaly/ Pallor/ Orthopnea
Kids: Non specific symptoms+ variable presentation
1. Freedman SB, Haladyn JK, Floh A, Kirsh JA, Taylor G, Thull-Freedman J. Pediatric myocarditis: emergency department clinical
findings and diagnostic evaluation. Pediatrics. 2007;120(6):1278–1285
2. Kim HJ, Yoo GH, Kil HR. Clinical outcome of acute myocarditis in children according to treatment modalities. Korean J Pediatr.
2010;53(7):745–752
3. English RF, Janosky JE, Ettedgui JA, Webber SA. Outcomes for children with acute myocarditis. Cardiol Young. 2004;14(5):488–493
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6. LAB EVALUATION
Non specific:
Raised WBCs/ Inflammatory markers/ Liver enzymes
Trop T+I:
Elevated as a marker of cardiac damage
Absence of increased value: Doesn’t rule out
Used as a differentiating tool b/w cardiac + non cardiac
causes of paediatric chest pain
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7. LAB EVALUATION CONT (TROPONINS)…
50% with raised Troponin—> Ultimately have cardiac disease
27%—> Myocarditis
0.052-0.088 ng/ml—> Cutoff (Trop T)
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8. NATRIURETIC PEPTIDES
High BNP: Helps in differentiation b/w HF + pul disease in kids
with RD
NT- Pro BNP:
Increased in both myocarditis+ idiopathic DCM
Levels higher in myocarditis at presentation, trends down
over time compared to DCM
Adults: Higher levels predictive of cardiac death/ transplant
Antibodies to cardiac proteins (myocin+ beta adr receptors):
Increased in adults
Kids: Unkown/ Experimental
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9. OTHER LAB INVESTIGATIONS…
EMB tissue: Gold standard
Cell culture/ PCR: Serum/ respi aspirate/ urine/ stool
Peripheral viral PCR: Co-relation with causative agents from
EMB—> Not established—> Evaluation complicated by
relatively high prevalence of commonly associated viruses in
general population
Mahfoud F, Gartner B, Kindermann M, et al. Virus serology in patients with suspected myocarditis: utility or futility? Eur Heart J.
2011;32(7):897–903
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10. ECG
Abnormal in majority—> So—> DO IT ALWAYS
Sinus tachycardia/ A+V Tachyarrhythmias
Low voltage complexes
Non- specific ST segment+ T wave abnormalities
Conduction delays/ Blocks (1/2/3rd D HB)—> May require
pacemakers in refractory cases
Mimics ACS: Adolescents+ young adults
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11. ECG
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12. CXR
Abnormal> 90%
Cardiomegaly—> MC
Not seen in those presenting with ACS like symptoms
Pulmonary edema/ pul infiltrate/ pleural effusion
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13. ECHO
Ventricular function+ dilatation—> Prognostic value
PE/ Intracavitary thrombi
Wall thickness/ wall motion abnormalities
Distinction of fulminant/acute (non fulminant myocarditis)/ DCM:
Acute myocarditis: Normal wall thickness, May have LV
dilatation
FM: Markedly dec systolic function, Ventricular
dysfunction: Global/ regional, normal chamber size, may
have inc IVS thickness due to myocardial edema
DCM: Markedly abnormal ventricular dilatation+
dysfunction
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14. ECHO CONT…
Severity of ventricular dysfunction—> Increased mortality+ requirement
of heart transplantation
Korean review:
72%: Dec EF
64%: Segmental wall abnormality
EF< 15%—> More persistent severe cardiac failure
RV dysfunction: Independent predictor of adverse outcome
Diastolic dysfunction even in presence of normal systolic function
Kim HJ, Yoo GH, Kil HR. Clinical outcome of acute myocarditis in children according to treatment modalities. Korean J Pediatr. 2010;53(7):745–
752
Mendes LA, Dec GW, Picard MH, Palacios IF, Newell J, Davidoff R. Right ventricular dysfunction: an independent predictor of adverse outcome in
patients with myocarditis. Am Heart J. 1994;128(2):301–307
Khoo NS, Smallhorn JF, Atallah J, Kaneko S, Mackie AS, Paterson I. Altered left ventricular tissue velocities, deformation and twist in children and
young adults with acute myocarditis and normal ejection fraction. J Am Soc Echocardiog. 2012;25(3):294–303.
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15. ECHO
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16. CMR
Non invasive gold standard for volumes+ function—> Prognostic
values
Tissue characterisation to evaluate hallmark of myocarditis:
Edema/ hyperemia/ fibrosis/ scarring
T2 weighted images: Edema, PE
T1 weighted images: Hyperemia/ inflammation
LGE images: Fibrosis/ scar—> No differentiation b/w
acute+ chronic inflammation
Sn: 67%; Sp: 91%
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17. LAKE LOUISE CRITERIA
17

18. CMR CONT…
Use in differentiation b/w myocarditis vs MI due to CAD:
Myocarditis LGE enhancement: Subepicardial/ transmural/
pathcy
MI LGE enhancement: Subendocardial/ transmural/
distribution in coronary perfusion territory
Repeat CMR b/w 1-2 weeks after disease onset: If non
diagnostic CMR changes early ds course, but high clinical
suspicion
Extent of LGE decreases over time—> Scar contraction
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19. EMB: GOLD STANDARD
DALLAS CRITERIA
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20. EMB: IS IT REALLY GOLD STANDARD??
Limitations:
Patchy tissue involvement
Preferential LV involvement
Difference in inter observer expert interpretation of
histopath samples
Apparent lack of correlation b/w outcomes/ response to
therapy
Baughman KL. Diagnosis of myocarditis: death of Dallas criteria. Circulation. 2006;113(4):593–595
Shanes JG, Ghali J, Billingham ME, et al. Interobserver variability in the pathologic interpretation of endomyocardial
biopsy results. Circulation. 1987;75(2):401–405.
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21. AHA/ ACC/ESC 2007 GUIDELINES
No recommendation for routine EMB for suspected myocarditis
Specific scenarios in which EMB is indicated—> Suspicion of
GCM:
1. New onset HF< 2 weeks duration+ Normal sized/ dilated
LV+ Heamodynamic compromise
2. New onset HF > 2weeks duration+ Dilated LV+
Ventricular arrhythmias/ HB+ Failure to respond to usual
care in 1-2 wks
Cooper LT, Baughman KL, Feldman AM, et al. The role of endomyocardial biopsy in the management of
cardiovascular disease: a scientific statement from the American Heart Association, the American College of
Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart
Failure Association of the European Society of Cardiology. Eur Heart J. 2007;28(24):3076–3093
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22. 3 TIER CLASSIFICATION: SAGAR ET AL.
MAYO CLINIC… (LANCET- 2012)
Possible subclinical acute myocarditis:
No symptoms+ Elevated biomarkers/ Abnormal ECG of CV
injury/ Abnormal cardiac function by ECHO or CMR
Probable acute myocarditis:
Symptoms+ Any 1/4 of above
Definitive myocarditis:
Histological/ Immunohistological evidence by EMB
Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet. 2012;379(9817):738–747
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23. TREATMENT…

24. TREATMENT…
Activity restriction
Medical management
Immunomodulators, Immunosuppressors
Antivirals
Mechanical circulatory supports
Survival and heart transplantation
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25. ACTIVITY RESTRICTIONS
2005 Bethesda guidelines: Pt should be restricted from all
competitive sports for 6 months after diagnosis
Athletes to return after normalisation of LV function+ size,
absence of arrhythmias on Holter+ exercise testing,
normalization of biomarkers, normalisation of all but relatively
minor ECG changes
Recommendations based on myocarditis found in athletes with
sudden death
Maron BJ, Ackerman MJ, Nishimura RA, Pyeritz RE, Towbin JA, Udelson JE. Task Force 4: HCM and other cardiomyopathies,
mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol. 2005;45(8):1340–1345
Harmon KG, Drezner JA, Maleszewski JJ, et al. Pathogeneses of sudden cardiac death in national collegiate athletic association
athletes. Circ Arrhythm Electrophysiol. 2014;7(2):198–204
Maron BJ, Doerer JJ, Haas TS, Tierney DM, Mueller FO. Sudden deaths in young competitive athletes: analysis of 1866 deaths
in the United States, 1980–2006. Circulation. 2009;119(8):1085–1092.
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26. MEDICAL MANAGEMENT
Main treatment: Supportive+ symptomatic care
80% pts: Require ICU admission
Diuretics/ ACEI/ ARBs/ B- Blockers
ACEI/ ARBs: Decreased myocardial fibrosis, inflammation,
autoantibody production
Adult study: Lack of B-Blocker therapy—> Greater risk of death/
transplantation
Carvidelol: Anti- inflammatory+ antiviral effects (Murine)
Metoprolol: Less robust response
Kindermann I, Kindermann M, Kandolf R, et al. Predictors of outcome in patients with suspected myocarditis. Circulation.
2008;118(6):639–648
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27. MEDICAL MANAGEMENT CONT…
CCBs: Decrease in inflammatory cytokines+ increased survival
(Murine)—> Effects on production of NO
IMAC-2 Trial: Adults/ 373 pts/ 12 centers/ 2014:
> 90% patients received ACEI/ ARBs+ B-Blockers—>
94%: Transplant free survival, 88%: HF hospitalization free
survival on 1 year follow up
Similar data in kids—> Limited
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28. RHYTHM ISSUES
Digoxin: Not recommended: Evidence of worsening viral
myocarditisibn murine models—> Increased mortality+
cytokines
Matsumori A, Igata H, Ono K, et al. High doses of digitalis increase the myocardial production of proinflammatory cytokines and
worsen myocardial injury in viral myocarditis: a possible mechanism of digitalis toxicity. Jpn Circ J. 1999;63(12):934–940
Amiodarone: Inhibits IL6 production, better survival (Murine)
Ito H, Ono K, Nishio R, Sasayama S, Matsumori A. Amiodarone inhibits interleukin 6 production and attenuates myocardial injury
induced by viral myocarditis in mice. Cytokine. 2002;17(4):197–202
40 kids with CHB:
27%—> PPI for prolonged HB
67%—> Resolution (Av: 3.3 days)
Batra AS, Epstein D, Silka MJ. The clinical course of acquired complete heart block in children with acute myocarditis. Pediatr
Cardiol. 2003;24(5):495–497
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29. ANTI VIRAL THERAPY
Ribavarin+ IFN- alpha:
Suppresses coxsackie virusin infected cultured human
myocardial cells/ Entero virus: Improvement in function and
viral clearance
IFN- beta:
Entero/ adenovirus—> Elimination of virus+ improvement in
LV systolic function at 6 Mts follow up
Pleconaril:
Prevents binding of coxsackie virus to cell receptor CAR
Ganciclovir+ Cidofovir:
CMV infected—> Reduction in myocarditis
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30. IMMUNO MODULATORS & SUPPRESSORS
Both inflammatory+ AI mediated cellular damage
IVIG:
Anti inflammatory+ immunomodulatory effects
2g/ kg IV
Significantly improved functions+ dimensions+ survival
Steroids,Usually in combination with cyclosporin/ azathioprine:
Improvement in inflammation on EMB follow up
Some also had recurrence of symptoms after
discontinuation of therapy
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31. IMMUNOADSORPTION
Antibody production+ antibody mediated cell signaling—>
Participate in myocardial damage
Role of immunoadsorption for antibody removal—> Increased
LV EF+NCI on follow up
IgG3: Role in complement activation—> Reduction
Staudt A, Bohm M, Knebel F, et al. Potential role of autoantibodies belonging to the immunoglobulin G-3 subclass in cardiac
dysfunction among patients with dilated cardiomyopathy. Circulation. 2002;106(19):2448–2453.
31

32. GCM+ EOSINOPHILIC MYOCARDITIS
Use of immunosuppressant therapy well established
EM: Reduced exposure to inciting exposure/ toxin+ steroids
GCM: Steroids+ cyclosporin/ azathioprine—> Av transplant free
survival of 12.3 months compared to only 3 months in untreated
patients
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33. MECHANICAL CIRCULATORY SUPPORT
For refractory heart failure, bridge to recovery/ heart transplant
ECMO/ VAD
Significant morbidity:
Major bleeding: 42-50%
Infection: 50-63%
Stroke: 29%
Fraser CD Jr, Jaquiss RD, Rosenthal DN, et al. Prospective trial of a pediatric ventricular assist device. N Engl J Med.
2012;367(6):532–541
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34. SURVIVAL+ HEART TRANSPLANTATION
Overall transplant free survival: 88%
Transplantation: 4.1%-18%
Myocarditis patients have worse post transplant survival
compared to other DCMs—> 2.7 x Increased mortality risk
Cause of death: Rejection
Cause: Persistence of infectious and/ or immune mechanisms
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35. TAKE HOME MESSAGE
Despite controversies in use of immunosuppression+ anti viral
therapy—> Primary therapy remains supportive care
Long term outcomes in kids still lacking
Late cardiac effects of childhood myocarditis: Still poorly
understood
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36. THANK YOU
Joseph Friedrich Sobernheim