Sritharan Shanathan, Murray Kindelan, Lam Dominic, Wittaker Daniel, Sverdlov Aaron, Boyle Andrew, Davies Allan, Williams Trent, Collins Nicholas
Cardiology Department, John Hunter Hospital Newcastle, Newcastle, New South Wales, Australia.
School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.
Intern Med J. 2025 Mar;55(3):474-482. doi: 10.1111/imj.16617. Epub 2025 Jan 8.
Clozapine has demonstrated superiority in improving both positive and negative symptoms of treatment-resistant schizophrenia; however, there are associated treatment-limiting side effects, including myocarditis, cardiomyopathy and agranulocytosis.
This retrospective cohort study describes the prevalence of myocarditis, left ventricular (LV) dysfunction, cardiovascular risk factors and outcomes in a cohort of patients maintained on clozapine therapy.
Data were retrospectively collated from patients who had a diagnosis of schizophrenia, had been managed with clozapine at any stage during their care and undergone at least one echocardiogram.
Between March 2020 and September 2021 674 patients were identified, 71% were male, with a mean age of 47 years old (interquartile range (IQR) 40-57). The mean duration of clozapine use was 7 years (IQR 4-13). The overall mortality was 5.54% during the follow-up period. Myocarditis was identified in one patient (0.15%) within the first 30 days, and an additional five cases were identified over the follow-up period (0.89%). The combined incidence of heart failure (HF) and myocarditis was 1.6% during the follow-up period. There was no association between LV size and function at baseline or during follow-up and adverse cardiac outcomes (comprising death, myocarditis, HF). Older age at initiation of therapy and baseline E/e' ratio were associated with risk of HF and myocarditis.
The overall incidence of myocarditis and HF during follow-up was low, with surveillance echocardiography offering limited predictive value. Patients maintained on clozapine are at risk of significant cardiovascular sequelae, likely reflecting an adverse risk factor profile.
氯氮平在改善难治性精神分裂症的阳性和阴性症状方面已显示出优越性；然而，存在相关的限制治疗的副作用，包括心肌炎、心肌病和粒细胞缺乏症。
这项回顾性队列研究描述了一组接受氯氮平治疗的患者中心肌炎、左心室（LV）功能障碍、心血管危险因素及转归的患病率。
回顾性整理诊断为精神分裂症、在其治疗的任何阶段接受氯氮平治疗且至少进行过一次超声心动图检查的患者的数据。
在2020年3月至2021年9月期间，共纳入674例患者，71%为男性，平均年龄47岁（四分位间距（IQR）40 - 57岁）。氯氮平的平均使用时长为7年（IQR 4 - 13年）。随访期间的总死亡率为5.54%。在最初30天内有1例患者（0.15%）被诊断为心肌炎，在随访期间又发现另外5例（0.89%）。随访期间心力衰竭（HF）和心肌炎的合并发生率为1.6%。基线或随访期间左心室大小和功能与不良心脏转归（包括死亡、心肌炎、HF）之间无关联。治疗起始时年龄较大及基线E/e'比值与HF和心肌炎风险相关。
随访期间心肌炎和HF的总体发生率较低，监测性超声心动图的预测价值有限。接受氯氮平治疗的患者有发生严重心血管后遗症的风险，这可能反映了不良的危险因素谱。
