Treatment of acute inflammatory cardiomyopathy with intravenous immunoglobulin ameliorates left ventricular function associated with suppression of inflammatory cytokines and decreased oxidative stress

Abstract

Although an autoimmune mechanism has been postulated for myocarditis and dilated cardiomyopathy, immunosuppressive agents had not been shown to be effective. Potential benefits of intravenous immunoglobulin (IVIg) in the therapy of patients with myocarditis and recent onset of dilated cardiomyopathy were reported. Also, experimental studies showed that IVIg is an effective therapy for viral myocarditis by antiviral and anti-inflammatory effects. Accordingly, in the current study, the effects of IVIg in the patients were investigated with the analyses of inflammatory cytokines and oxidative stress. Nine patients (six in myocarditis, three in acute dilated cardiomyopathy) were treated with high-dose intravenous IVIg (1-2 g/kg, over 2 days). All were hospitalized with New York Heart Association (NYHA) class III to IV heart failure, left ventricular ejection fraction (LVEF) <40%, and symptoms for <6 months at the time of presentation. Five patients were diagnosed using endomyocardial biopsy. LVEF determined by echocardiography improved from 19.0+/-7.5% (mean+/-S.D.) at baseline to 35.4+/-9.1% at follow up (12.2+/-5.8 days after the treatment) (P<0.01). C-reactive protein and plasma inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) were decreased by this treatment. In addition, plasma level of thioredoxin, which regulates the cellular state of oxidative stress, was decreased by the treatment. All nine patients improved functionally to NYHA class I to II, and were discharged without side-effects. There have been no subsequent hospitalizations for heart failure during the course of follow-up (3 months-4.5 years). LVEF improved 16% of EF in the patients with myocarditis and acute dilated cardiomyopathy with the reduction of cytokines associated with improvement of oxidative stress state by high-dose of IVIg. Thus, IVIg seems to be a promising agent in the therapy of acute inflammatory cardiomyopathy in view of not only suppression of inflammatory cytokines but a reduction of oxidative stress.