Intravenous immunoglobulin for presumed viral myocarditis in children and adults

 

Abstract

Background

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

To assess the effects IVIG in people with presumed myocarditis.

Search methods

We searched CENTRAL (2009, Issue 3), MEDLINE (1966-September 2009), EMBASE (1988-September 2009), CINAHL (1982-September 2009), Web of Science (1975-September 2009), LILACS (1982-September 2009), trials registries and conference proceedings. We contacted authors of trials and checked reference lists of relevant papers. No language restrictions were applied.

Selection criteria

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 6 months; (2) patients had no evidence of non-infectious or bacterial cardiac disease; and, (3) patients were randomized 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 6 months postpartum.

Data collection and analysis

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

Main results

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 6 and 12 months showed equivalent improvement in LVEF (mean difference 0.00, 95% CI -0.07 to 0.07 at 6 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).

Authors' conclusions

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.

 

Plain language summary

Intravenous immunoglobulin for presumed viral myocarditis in children and adults

Acute myocarditis involves inflammatory cell infiltration of the myocardium, and is thought to most commonly begin as a viral infection. The disease affects all ages. Based on multiple case reports and case series, IVIG has become part of routine practice for treating patients with acute myocarditis in many centers. Only one randomized controlled trial (RCT) was identified: this trial evaluated 62 adults with acute myocarditis and found no treatment benefit among patients receiving IVIG.

 

摘要

背景

靜脈內免疫球蛋白注射於疑似病毒性心肌炎之孩童及成人

病歷報告及病歷系列研究已經顯示，免疫球蛋白注射於疑似病毒性心肌炎之孩童及成人有明顯之療效。免疫球蛋白注射已成為處理此種狀況之常態性方式。

目標

為比較疑似病毒性心肌炎之病人，接受或不接受免疫球蛋白治療之結果差異。

搜尋策略

我們搜尋CENTRAL (2009, Issue 3)、 MEDLINE (1966 – September 2009)、 EMBASE (1988 – September 2009)、 CINAHL (1982 – September 2009)、 Web of Science (1975 – September 2009)、LILACS (1982 – September 2009)、試驗登錄中心及研討會手冊。 我們並與試驗作者聯絡，並檢查相關文章的參考文獻。不限定語言種類。

選擇標準

研究之選擇標準為:(1)病人之臨床診斷為急性心肌炎伴隨左心室射出率(LVEF，left ventricular ejection fraction)< = 0.45，LVEDD大於正常值之二倍標準差，或是縮短分率(shortening fraction, SF)小於平均值之兩倍標準差，且其心臟症狀之發病期間小於六個月；(2)無證據顯示病人有非感染性之心臟病或細菌性之心臟病；並且 (3)病人隨機分配為接受至少1gm/kg之免疫球蛋白，和不接受免疫球蛋白或接受安慰劑者做比較。 研究之排除標準為：(1)病人曾於結果分析前接受免疫抑制劑；或是(2)心肌炎初始發病期間為分娩後之六個月內。

資料收集與分析

兩位獨立檢閱人完成資料之篩選及選入標準。兩位檢閱人使用Jadad scale及遮盲(allocation concealment)方式進行品質分析。兩位獨立檢閱人進行資料擷取工作。因為只找到一篇相關研究故無法進行統合分析(Metaanalysis)。

主要結論

相關研究收入62位急性心肌炎之成人，以隨機且設盲的方式分配，接受免疫球蛋白或相等容積之0.1%白蛋白。兩組之死亡、需心臟移植，及需置放左心室輔助器之發生率皆低(對於無事故存活率(eventfree survival rate)之勝算比為0.52，95%信賴區間0.12至2.30)。分別追蹤發病後6個月及12個月顯示左心室射出率(LVEF)有同等之進步(6個月之平均值之差異0.00，95%信賴區間−0.07至0.07；12個月之平均值之差異0.01，95%信賴區間−0.06至0.08)。利用尖峰氧氣消耗(peak oxygen consumption)評估其心臟功能顯示兩組在第12月時之功能相等(平均值之差異−0.80，95%信賴區間4.57至2.97)。靜脈輸注相關之副作用於實驗組較常見，但其嚴重程度皆屬輕微(勝算比為30.16，95%信賴區間1.69至539.42)。

作者結論

由試驗而來之證據並未支持使用免疫球蛋白來治療成人疑似病毒性心肌炎。目前仍未發表使用於孩童之隨機試驗。更深入之病生理研究將有助於診斷標準的進步，此亦有助於未來研究之進展。

翻譯人

本摘要由臺北榮民總醫院葉哲廷翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

目前由隨機試驗得來之證據並未支持使用靜脈注射免疫球蛋白來治療疑似病毒性心肌炎。急性心肌炎牽涉到免疫細胞於心肌之浸潤，這被視為病毒感染常見的初始表現。這個疾病涵蓋所有的年齡層。基於多數的病例報告及病例系列研究之結果，許多醫學中心採用免疫球蛋白來治療急性心肌炎，這已是臨床執業上的常規作法。目前只有ㄧ隨機控制試驗(RCT)被找出來：這試驗評估了62位患有急性心肌炎之成人，其結果顯示接受免疫球蛋白是沒有助益的。