**7. Outcome**

56 Myocarditis

course of the disease. Therefore, studies assessing immunomodulation and immune suppressive agents were problematic to decode into an applicable, routine treatment for children and adults with acute myocarditis. One should also consider that initiating agents for acute myocarditis and following clinical course may change from time to time and by geographic site. Although such a controversy remains to be settled, IVIG may be used only

While viral infection is the most frequent cause of myocarditis, it might be possible to think that vaccines and antiviral agents might be helpful in the treatment of myocarditis. It is obvious that studies using polymerase chain reaction identified viral genomes in patients with acute myocarditis (Bowles et al., 2003). Bu, there are a few studies which demonstrated that requirement for transplantation and mortality was not dependent on the presence of viral genome (Kindermann et al., 2008, Kuhl et al., 2005). So, many investigators suggested that the presence of viral antigens or nucleotides in the myocardium alone is not satisfactory to prove that the virus is the cause of myocarditis (Matsumori et al., 2007). Since the diagnosis of viral myocarditis is frequently challenging and the diagnostic approaches have not been established or standardised, the number of clinical trials for virus proven myocarditis is limited. For that reason, in order to investigate therapeutic and preventative methods for myocarditis, various animal models have been developed. Several promising new agents including peroxisome proliferator activated gamma receptor activator, rapamycine, pycogenol, SUNC8079 and mycophenol mofetil have been studied in murine models of myocarditis during the last decade (Komiyoshi et al., 2005, Ellis&DiSalvo, 2007, Matsumori, 2007). It has been demonstrated that these agents decrease the severity of myocarditis and improve cardiac function, blocks activation of NF-κ, blocks mRNA expression of key cytokines (IL-1, IL-6 and TNF) and stabilizes mast cell (Matsumori, 2007). Synergistic effect of IFN- α and ribavirin has been demonstrated against both EMCV and coxsackie virus infection (Okada et al., 1992, Matsumori, 2007). IFN- β has reported to be effective in studies including small number of patients with left ventricular dysfunction whose biopsy specimens were positive for adenovirus or enterovirus (Kuhl et al., 2003). Although various strategies for the prevention of acute myocarditis have been studied in murine models, up to now, there have been no vaccination trial in humans. Vaccination against mumps, rubella, poliomyelitis, measles and influenza has made myocarditis consequent to these infections quite rare and increases the arguments on whether vaccination against other cardiotropic viruses might prevent myocarditis in the future. A classical example in this regard was supported by the study of EFE described previously (Ni et al., 1997). The mumps virus vaccine has entirely eliminated this form of dilated cardiomyopathy. It is unlikely that antiviral vaccines to battle this disease will be improved

Recommendations concerning physical activity affirm that all patients with presumed or definite myocarditis discontinue competitive sports and undergo a prudent convalescence period around six months after the onset of clinical manifestations. Athletes may return to sports activity if LV function, dimensions and wall motions return to normal, markers of inflammation in blood have resolved, 12-lead ECG has normalized and clinically relevant

arrhythmias are absent on Holter ECG or graded exercise testing (Maron et al., 2005).

in selected pediatric patients with acute myocarditis.

in the near future due to low incidence of the disease.

**6.3 Physical activity** 

**6.2 Antiviral treatment & vaccines** 

Prognosis of myocarditis is as changed as its clinical presentations. Although the fewer data are available on the natural history of myocarditis in children, it is proposed that the outcomes in pediatric patients presenting with acute heart failure secondary to acute myocarditis tends to be more positive than the prognosis with dilated cardiomyopathy (Drucker et al., 1994, Lee et al., 1999). In a retrospective analysis of 36 children with histologically proven lymphocytic myocarditis (Lee et al., 1999), excellent outcomes have been demonstrated in children with myocarditis, especially those surviving 72 hours after presentation. Gagliardi and colleagues, classified 114 children into three groups as acute myocarditis, borderline myocarditis and non-inflammatory cardiomyopathy according to histological analysis (Gagliardi et al., 2004). Best survival rate (97%) was found in acute myocarditis group. They suggested that this high long term survival rate of this cohort may be due to effect of short term immunosuppressive therapy. On the other hand, in a multicenter study including children and adults, difference in outcomes between age groups was noted (Bowles et al., 2003). Survival rate for neonates and infants (33 and 45%, respectively) were significantly lower than the other groups. Survival rate was noted to be greatest in adolescent age group. A retrospective study involving 28 children with acute myocarditis, analysed the predictors of outcome. It was observed that ejection fraction < 30%, shortening fraction < 15%, left ventricle dilatation and moderate to severe mitral regurgitation at admission were associated with poor outcome (Kuhn et al., 2004). However, it was understood from the findings of adult trials that syncope, right ventricle dysfunction, elevated pulmonary artery pressure and advanced New York Heart Association functional class were predictors of increased probability of death or requirement for transplantation (Mendes et al, 1994, McCarthy et al., 2000, Magnani&Dec, 2006, Kindermann et al., 2008). Histological classification and severity of symptoms may also give a clue about prognosis. Giant cell myocarditis has a chance of 89% of death or transplantation. Surprisingly, acute fulminant myocarditis may have a better prognosis (Ellis & DiSalvo, 2007).

In general, transplantation is needed in 1-8% of patients with acute myocarditis (Ellis & DiSalvo, 2007). In spite of severe disease at presentation, there is a probability of improvement. Patients should not be listed promptly unless recovery is believed extremely unlikely despite judicious management.
