Wang Zhiyuan, Xiao Yanyan, Wen Haichu, Yang Yifei, Yuan Meng, Jiao Meng, Gu Yan, Jin Mei, Du Jie
Department of Pediatric Heart Centre, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Beijing Pediatric Heart Centre, Beijing, China.
Sci Rep. 2025 May 12;15(1):16437. doi: 10.1038/s41598-025-96184-3.
The response of pediatric dilated cardiomyopathy (PDCM) patients to intravenous immune globulin (IVIG) varies from cardiac functional recovery to heart transplantation and even death. IVIG therapy can significantly improve the left ventricular ejection fraction (LVEF) in some PDCM patients, but indicators for evaluating the response to IVIG therapy are lacking. Lipid metabolic disturbance is associated with changes in cardiac function, but no studies have examined the associations between lipidomics markers and the efficacy of IVIG. Discovery analyses were based on 322 targeted lipids in a retrospective cohort study. T tests, orthogonal‒orthogonal projections to latent structures discriminant analysis (OPLS-DA) and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined via Cox proportional hazards regression models. We subsequently developed a score for the candidate lipid metabolites, which was then used to classify children into two groups (0-3 and 4), and the survival curves of the two groups were drawn. There were 31 patients in the discovery set and 24 patients in the validation set. Adverse events which were defined as death, heart transplant, and rehospitalization for HF were observed in 23 patients (41.8%). After adjusting for age, LVEF, and the LV end-diastolic diameter z score, CE-16:1, PE36:4p, PE40:6p, and PE40:6p (22:6) were significantly associated with the occurrence of adverse events in the discovery set. The results were also consistent in the validation set, and the hazard ratios (HRs) were 2.638 (95% CI 1.042-6.683; p = 0.041), 0.549 (95% CI 0.340-0.886; p = 0.014), 0.271 (95% CI 0.109-0.672; p = 0.005), and 0.299 (95% CI 0.121-0.741; p = 0.009), respectively. We developed a score for these four lipid metabolites. When the score reached 4, adverse events were more likely to be observed in both sets. Serum lipid metabolites can be used to predict the efficacy of IVIG in children with DCM.
小儿扩张型心肌病（PDCM）患者对静脉注射免疫球蛋白（IVIG）的反应各不相同，从心功能恢复到心脏移植甚至死亡。IVIG治疗可使部分PDCM患者的左心室射血分数（LVEF）显著提高，但目前缺乏评估IVIG治疗反应的指标。脂质代谢紊乱与心功能变化有关，但尚无研究探讨脂质组学标志物与IVIG疗效之间的关联。在一项回顾性队列研究中，基于322种靶向脂质进行探索性分析。采用t检验、正交信号校正的正交偏最小二乘法判别分析（OPLS-DA）和随机森林（RF）分析筛选候选脂质。通过Cox比例风险回归模型检验候选脂质的关联性。随后，我们为候选脂质代谢物制定了一个评分，用于将儿童分为两组（0 - 3分和4分），并绘制两组的生存曲线。探索集有31例患者，验证集有24例患者。23例患者（41.8%）出现了定义为死亡、心脏移植和因心力衰竭再次住院的不良事件。在调整年龄、LVEF和左心室舒张末期直径z评分后，CE-16:1、PE36:4p、PE40:6p和PE40:6p（22:6）与探索集中不良事件的发生显著相关。验证集的结果也一致，风险比（HR）分别为2.638（95%CI 1.042 - 6.683；p = 0.041）、0.549（95%CI 0.340 - 0.886；p = 0.014）、0.271（95%CI 0.109 - 0.672；p = 0.005）和0.299（95%CI 0.121 - 0.741；p = 0.009）。我们为这四种脂质代谢物制定了一个评分。当评分达到4分时，两组中更有可能观察到不良事件。血清脂质代谢物可用于预测IVIG治疗儿童DCM的疗效。
