Intravenous immunoglobulin for presumed viral myocarditis in children and adults

Acute myocarditis is inflammation of the heart and is thought to be most commonly begin as a viral infection. The disease affects individuals of all ages. On the basis of multiple case reports and case series, intravenous immunoglobulin (IVIG) has become part of routine practice for treating adults and children with acute myocarditis at many centres. This is an update of a previous review, which found only one randomised trial of 62 adults, suggesting that IVIG is not useful in myocarditis. A second trial was added with this update. This trial evaluated 83 children who had the relatively rare combination of myocarditis and encephalitis (inflammation of the brain). Investigators found a lower death rate among children receiving IVIG than in those who did not, but this study had high risk of bias. More study is required before IVIG can be routinely recommended for adults or children with myocarditis.

Authors' conclusions: 

Evidence from one trial does not support the use of IVIG for the treatment of adults with presumed viral myocarditis. The only paediatric trial had high risk of bias but suggested that benefit may be seen in the select group of children beyond the neonatal period who have viral encephalitis with myocarditis. Until higher-quality studies have demonstrated benefit in a particular group of patients, IVIG for presumed viral myocarditis should not be provided as routine practice in any situation. Further studies of the pathophysiology of myocarditis would lead to improved diagnostic criteria, which would facilitate future research.

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Background: 

This is an update of a previous review. Case reports and case series have described dramatic responses to intravenous immunoglobulin (IVIG) in people with presumed viral myocarditis, and its administration has become commonplace.

Objectives: 

The primary objective of this review was to compare transplant-free survival of adults and children with presumed viral myocarditis treated with IVIG versus those who did not receive IVIG. A secondary objective was to determine if a group of patients with presumed viral myocarditis could be identified (on the basis of age, duration of symptoms, acuity of onset of symptoms, cardiac function at presentation, virological results or the presence or absence of histological evidence of acute myocarditis on cardiac biopsy in patients in whom a biopsy was performed) who would be the most likely to benefit from IVIG.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 12 of 12), the Database of Abstracts of Reviews of Effects (DARE) (2013, Issue 4 of 4), MEDLINE (Ovid, 1946 to January Week 3 2014), EMBASE (Ovid, 1980 to Week 4 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Web of Science (Thomson Reuters, 1970 to 24 January 2014), the Latin American and Caribbean Health Science Information Database (LILACS) (1982 to 30 January 2014), trials registries and conference proceedings. We contacted authors of trials and checked reference lists of relevant papers. We applied no language restrictions.

Selection criteria: 

We included studies if (1) participants had a clinical diagnosis of acute myocarditis with a left ventricular ejection fraction (LVEF) ≤ 0.45, left ventricular end-diastolic diameter (LVEDD) > 2 standard deviations (SDs) above the norm or a shortening fraction (SF) > 2 SDs below the mean with duration of cardiac symptoms < 6 months; (2) participants had no evidence of non-infectious or bacterial cardiac disease; and (3) participants were randomly assigned to receive at least 1 g/kg of IVIG versus no IVIG or placebo. We excluded studies if (1) participants had received immunosuppression before outcome assessment; or (2) onset of myocarditis was reported to occur < 6 months post partum.

Data collection and analysis: 

Two review authors screened searches and extracted data independently. We assessed quality using the 'Risk of bias' tool. Meta-analysis was not possible because only two relevant studies were found, and researchers analysed markedly different populations.

Main results: 

In this update, review authors added one study to the study from the original review. The first relevant study involved 62 adults with recent-onset dilated cardiomyopathy randomly assigned to receive IVIG or an equivalent volume of 0.1% albumin in a blinded fashion. The overall risk of bias was unclear. The incidence of death or the requirement for cardiac transplant or placement of a left ventricular assist device was low in both groups (odds ratio (OR) for event-free survival 0.52, 95% confidence interval (CI) 0.12 to 2.30). Follow-up at six months and at 12 months showed equivalent improvement in LVEF (mean difference (MD) 0.00, 95% CI -0.07 to 0.07 at six months; MD 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 (MD -0.80, 95% CI -4.57 to 2.97). Infusion-related side effects were more common in the treated group, but all were reported to be mild (OR 30.16, 95% CI 1.69 to 539.42).

The second study added at this update included 83 children in India with suspected viral encephalitis and myocarditis. The overall risk of bias was high. The odds ratio for event-free survival was 7.39 (95% CI 0.91 to 59.86). Follow-up occurred only until hospital discharge, and LVEF was 49.5% in the treated group versus 35.9% in the placebo group (risk difference 13.6%, 95% CI 5.1 to 22.1%; P value = 0.001).

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