Intravenous immunoglobulin for presumed viral myocarditis in children and adults.

backgroundThis 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.

objectivesThe primary objective of this review was to compare event-free (death, requirement for a cardiac transplant, or placement of a left ventricular assist device) or overall (death) 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

methodsWe searched CENTRAL, MEDLINE, Embase, DARE, CINAHL, Web of Science Core Collection, and LILACS in July 2019, and two trial registries in November 2019. 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 left ventricular shortening fraction (LVSF) > 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 have occurred < 6 months postpartum. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and extracted data. We assessed risk of bias with the Cochrane 'Risk of bias' tool. We conducted meta-analysis for two outcomes (overall survival and improvement in LVEF) with two adult trials. Other meta-analyses were not possible because only three relevant trials were included, and researchers analysed markedly different populations and used different outcome measures. MAIN

resultsIn this update we added two trials to the two previously included trials. A quasi-randomised trial was previously included due to a paucity of evidence from randomised trials; however, with the addition of two new randomised trials, it was removed from this update. For two adult trials, the overall risk of bias was unclear with very low-certainty evidence for all outcomes. The first trial studied 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 effect on event-free survival between groups was uncertain (risk ratio (RR) of any event 1.76, 95% confidence interval (CI) 0.48 to 6.40). The second trial studied 41 adults with acute myocarditis randomised to either high-dose IVIG (1 to 2 g/kg over two days) or no treatment. The IVIG group reported greater survival time after 60 days (no raw data, P < 0.01), but the evidence is uncertain. We pooled the reported number of deaths in both trials, with no evidence of a difference between groups (RR 0.91, 95% CI 0.23 to 3.62, I