**5.1.2 Ventricular assist system**

There is the risk of severe pulmonary congestion due to PCPS in cases of extreme deterioration of left ventricular function. In such cases, the patient should be switched to a ventricular assist system (VAS) before organ dysfunction develops. Grinda et al. (2004) reported that they introduced VAS in five cases of severe fulminant myocarditis and obtained good outcomes. Recently, the clinical effectiveness of modified VAS using an extracorporeally established centrifugal pump was advocated by John et al. (2007) in the United States. Modified VAS has combined the advantages of minimally invasive extracorporeal membrane oxygenation and high efficiency.

### **5.2 Immunoregulation therapy**

Generally, the time limit for continuous mechanical circulatory support, including PCPS or VAS, is approximately 1 week. We withdraw the system even if recovery from circulatory failure is incomplete. In such cases, introduction of immunoregulation therapy is discussed. Many case reports have asserted the effectiveness of immunoregulation therapy. Although there is no established evidence, we believe that immunoregulation is acceptable in intractable cases because no radical treatments are presently available.

### **5.2.1 High-dose γ-globulin**

The effectiveness of high-dose γ-globulin was reported by Takada et al. (1995). It is expected that γ-globulin counteracts the actions of the infective viruses and reduces suppression of cardiac function by inflammatory cytokines during the acute phase. γ-Globulin intensifies patients' immune competence, and therefore complications, such as an infection compromised by steroid administration, do not take hold. The mechanisms of high-dose administration have not been completely clarified, although several hypotheses have been suggested: (1) it functions as a neutralizing antibody; (2) it has an anti-inflammatory effect, reducing the release of inflammatory cytokines induced by a combination of the Fc part of γglobulin and the suppressive Fc receptor of macrophages; and (3) it has the effect of antiactivation on activated complement (Rosen, 1993). However, it is not strongly recommended because there is no evidence that has been confirmed by large clinical trials. Finally, cardiac function has not recovered in several cases with its use.

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#### **5.2.2 High-dose steroids**

The effectiveness of steroids as anti-inflammatory and immunosuppressant drugs has been widely accepted. Its effectiveness when treating patients with fulminant myocarditis has been also reported in many studies (Ino et al., 1995). However, administration of steroid was not proved effective in patients with lymphocytic myocarditis in a clinical trial (Mason et al., 1995). We would not hastily administer steroids to patients with acute-phase myocarditis with a suspected viral infection. On the other hand, it is expected that administration of steroids alleviates cardiac dysfunction in patients with giant cell myocarditis and eosinophilic myocarditis (Cooper et al., 1997). Particularly, high-dose steroids should be given prior to other treatments in patients with the fulminant type of giant cell myocarditis.
