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.

氯氮平与心肌炎的风险增加有关。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，哪些体征、症状和检查对于区分心肌炎和氯氮平的良性不良反应很重要，尚不确定。澄清这个问题很重要，因为错过心肌炎的诊断或不必要地停用氯氮平都可能产生毁灭性的后果。

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和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的患者实例。然后对每个疑似病例的患者的匿名病例记录进行人工检查，并将那些病例模糊的病例转介给最多三名心脏病专家进行独立评估。将疑似病例患者分为确诊心肌炎、排除心肌炎或未确定心肌炎。

在 228 名疑似心肌炎患者的 254 例中，11.4%（ n = 29 例）被确诊为疑似心肌炎。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），而心动过速的诊断价值不大。所有确诊病例均发生在开始使用氯氮平后 42 天内。

怀疑心肌炎可能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。