Clozapine is associated with increased risk of myocarditis. However, many common side-effects of clozapine overlap with the clinical manifestations of myocarditis. As a result, there is uncertainty about which signs, symptoms and investigations are important in distinguishing myocarditis from benign adverse effects of clozapine. Clarity on this issue is important, since missing a diagnosis of myocarditis or discontinuing clozapine unnecessarily may both have devastating consequences.

To examine the clinical characteristics of clozapine-induced myocarditis and to identify which signs and symptoms distinguish true myocarditis from other clozapine adverse effects.

A retrospective analysis of the record database for 247 621 patients was performed. A natural language processing algorithm identified the instances of patients in which myocarditis was suspected. The anonymised case notes for the patients of each suspected instance were then manually examined, and those whose instances were ambiguous were referred for an independent assessment by up to three cardiologists. Patients with suspected instances were classified as having confirmed myocarditis, myocarditis ruled out or undetermined.

Of 254 instances in 228 patients with suspected myocarditis, 11.4% (n = 29 instances) were confirmed as probable myocarditis. Troponin and C-reactive protein (CRP) had excellent diagnostic value (area under the curve 0.975 and 0.896, respectively), whereas tachycardia was of little diagnostic value. All confirmed instances occurred within 42 days of clozapine initiation.

Suspicion of myocarditis can lead to unnecessary discontinuation of clozapine. The ‘critical period’ for myocarditis emergence is the first 6 weeks, and clinical signs including tachycardia are of low specificity. Elevated CRP and troponin are the best markers for the need for further evaluation.

氯氮平与心肌炎风险增加有关。然而，氯氮平的许多常见副作用与心肌炎的临床表现重叠。因此，对于区分心肌炎和氯氮平的良性不良反应，哪些体征、症状和检查很重要尚不确定。明确这个问题很重要，因为错过心肌炎的诊断或不必要地停用氯氮平可能都会产生毁灭性的后果。

检查氯氮平诱发的心肌炎的临床特征，并确定哪些体征和症状可区分真正的心肌炎与其他氯氮平不良反应。

对 247 621 名患者的记录数据库进行了回顾性分析。自然语言处理算法识别出疑似心肌炎患者的实例。然后手动检查每个疑似病例的患者的匿名病例记录，并将那些病例模棱两可的病例转介给多达三名心脏病专家进行独立评估。疑似病例的患者被归类为确诊心肌炎、排除心肌炎或未确定心肌炎。

在 228 例疑似心肌炎患者的 254 例中，11.4%（n = 29 例）被确认为可能的心肌炎。肌钙蛋白和 C 反应蛋白 (CRP) 具有极好的诊断价值（曲线下面积分别为 0.975 和 0.896），而心动过速几乎没有诊断价值。所有确诊病例均发生在开始使用氯氮平的 42 天内。

怀疑心肌炎可导致不必要地停用氯氮平。心肌炎出现的“关键期”是前 6 周，包括心动过速在内的临床症状特异性较低。CRP 和肌钙蛋白升高是需要进一步评估的最佳标志。