Intravenous immunoglobulin for presumed viral myocarditis in children and adults

Case reports and case series have described dramatic responses to IVIG in adults and children with presumed viral myocarditis. Administration of IVIG has become commonplace in the management of this condition.

To compare the outcome of patients with presumed viral myocarditis treated with IVIG to patients who did not receive IVIG.

We searched CENTRAL (Issue 2, 2003), MEDLINE/PubMed (1966-2003), EMBASE (1988-2003), CINAHL (1982-2003), Web of Science (1975-2003), trials registries and conference proceedings. We contacted authors of trials and checked reference lists of relevant papers.

Studies were included if: (1) patients had a clinical diagnosis of acute myocarditis with either a left ventricular ejection fraction (LVEF) <= 0.45, LVEDD of >2 SDs above the norm, or a shortening fraction (SF) >2 SDs below the mean and the duration of cardiac symptoms was less than six months; (2) patients had no evidence of non-infectious or bacterial cardiac disease; and, (3) patients were randomised to receive at least 1 gm/kg of IVIG versus no IVIG or placebo. Studies were excluded if: (1) patients had received immunosuppression prior to outcome assessment; or, (2) onset of myocarditis was less than six months postpartum.

Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted independently by two reviewers. Meta-analysis was not possible because only one relevant study was found.

The relevant study involved 62 adults with acute myocarditis randomized to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The incidence of death or requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (OR for event-free survival was 0.52 ,95% CI 0.12 to 2.30). Follow-up at six and 12 months showed equivalent improvement in LVEF (mean difference 0.00, 95% CI -0.07 to 0.07 at six months, mean difference 0.01, 95% CI -0.06 to 0.08 at 12 months). Functional capacity as assessed by peak oxygen consumption was equivalent in the two groups at 12 months (mean difference -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all appeared to be mild (OR 30.16, 95% CI 1.69 to 539.42).

Evidence from one trial does not support the use of IVIG for the management of adults with presumed viral myocarditis. There are no randomized paediatric trials. Further studies of the pathophysiology of this entity would lead to improved diagnostic criteria which would facilitate future research.