Mason J W, O'Connell J B, Herskowitz A, Rose N R, McManus B M, Billingham M E, Moon T E
Division of Cardiology, University of Utah, Salt Lake City.
N Engl J Med. 1995 Aug 3;333(5):269-75. doi: 10.1056/NEJM199508033330501.
Myocarditis is a serious disorder, and treatment options are limited. This trial was designed to determine whether immunosuppressive therapy improves left ventricular function in patients with myocarditis and to examine measures of the immune response as predictors of the severity and outcome of disease.
We randomly assigned 111 patients with a histopathological diagnosis of myocarditis and a left ventricular ejection fraction of less than 0.45 to receive conventional therapy alone or combined with a 24-week regimen of immunosuppressive therapy. Immunosuppressive therapy consisted of prednisone with either cyclosporine or azathioprine. The primary outcome measure was a change in the left ventricular ejection fraction at 28 weeks.
In the group as a whole, the mean (+/- SE) left ventricular ejection fraction improved from 0.25 +/- 0.01 at base line to 0.34 +/- 0.02 at 28 weeks (P < 0.001). The mean change in the left ventricular ejection fraction at 28 weeks did not differ significantly between the group of patients who received immunosuppressive therapy (a gain of 0.10; 95 percent confidence interval, 0.07 to 0.12) and the control group (a gain of 0.07; 95 percent confidence interval, 0.03 to 0.12). A higher left ventricular ejection fraction at base line, less intensive conventional drug therapy at base line, and a shorter duration of disease, but not the treatment assignment, were positive independent predictors of the left ventricular ejection fraction at week 28. There was no significant difference in survival between the two groups (P = 0.96). The mortality rate for the entire group was 20 percent at 1 year and 56 percent at 4.3 years. Features suggesting an effective inflammatory response were associated with less severe initial disease.
Our results do not support routine treatment of myocarditis with immunosuppressive drugs. Ventricular function improved regardless of whether patients received immunosuppressive therapy, but long-term mortality was high. Patients with a vigorous inflammatory response had less severe disease.
心肌炎是一种严重疾病，治疗选择有限。本试验旨在确定免疫抑制疗法是否能改善心肌炎患者的左心室功能，并研究免疫反应指标作为疾病严重程度和预后预测指标的情况。
我们将111例经组织病理学诊断为心肌炎且左心室射血分数低于0.45的患者随机分组，分别接受单纯常规治疗或联合为期24周的免疫抑制治疗方案。免疫抑制治疗包括泼尼松联合环孢素或硫唑嘌呤。主要结局指标是28周时左心室射血分数的变化。
在整个研究组中，平均（±标准误）左心室射血分数从基线时的0.25±0.01提高到28周时的0.34±0.02（P<0.001）。接受免疫抑制治疗的患者组在28周时左心室射血分数的平均变化（增加0.10；95%置信区间为0.07至0.12）与对照组（增加0.07；95%置信区间为0.03至0.12）相比，差异无统计学意义。基线时左心室射血分数较高、基线时常规药物治疗强度较低以及病程较短，但不是治疗分组情况，是28周时左心室射血分数的阳性独立预测因素。两组患者的生存率无显著差异（P = 0.96）。整个研究组1年时的死亡率为20%，4.3年时为56%。提示有效炎症反应的特征与初始疾病较轻有关。
我们的结果不支持用免疫抑制药物对心肌炎进行常规治疗。无论患者是否接受免疫抑制治疗，心室功能均有改善，但长期死亡率较高。炎症反应强烈的患者疾病较轻。
