Muschel Nadine, Höck Michaela, Griesmaier Elke, Azim Samira Abdel, Ralser Elisabeth, Schreiner Christina, Schermer Elisabeth, Kiechl-Kohlendorfer Ursula, Mutz-Dehbalaie Irene, Michel Miriam
Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Innsbruck, Austria.
Department of Paediatrics II (Neonatology), Medical University of Innsbruck, Innsbruck, Austria.
Front Pediatr. 2025 Aug 26;13:1649341. doi: 10.3389/fped.2025.1649341. eCollection 2025.
Mechanistic/mammalian target of rapamycin (mTOR) inhibitors have been used successfully to reduce the size of cardiac rhabdomyomas. However, the number of published cases is small and thus there is no consensus about therapeutic approaches, especially regarding dosing regimens and safety profiles of mTOR inhibitors. Based on a systematic literature review and one new case report, we discuss in detail the indication and adverse effects of fetal and neonatal mTOR-inhibitor therapy.
A comprehensive search was conducted on PubMed/MEDLINE and Web of Science for studies using combinations of the relevant medical subject heading (MeSH) terms and keyword (rhabdomyoma AND fetal OR fetus OR prenatal AND cardiac AND sirolimus) from the first report in 2018 until July 2025. Studies were included if they reported on pregnancies with fetal cardiac tumor and rhabdomyoma entity suspicion treated with mTOR inhibitors.
In total, 67 results were found. After excluding non-eligible publications, a total of 20 documented cases were identified from 15 reports, all presenting lifesaving effects of mTOR inhibitors in fetuses and neonates with cardiac rhabdomyomas. We report on a patient with a prenatally suspected cardiac rhabdomyoma, which, due to imminent bilateral outflow tract obstruction, was prenatally treated with sirolimus. Tumor regression could be achieved. For maternal medical reasons, prenatal sirolimus had to be stopped after 5 weeks. Postnatal incessant atrioventricular re-entrant tachycardia occurred, which was unresponsive to electric or medical cardioversion (amiodarone) and unresponsive to everolimus. The patient developed massive capillary leak syndrome within hours. In combination with restrictive ventricular filling properties, the tachycardia resulted in death on the seventh day of life.
Cardiac rhabdomyomas have the potential to become a life-threatening condition, not only by impairing myocardial function and cardiac outflow, but also by causing arrhythmia due to tumor muscle bundles as substrate for a pre-excitation syndrome resulting in intrauterine or postnatal atrioventricular re-entrant tachycardia, as observed in our patient. The pharmacological therapeutic approach is fetal and neonatal treatment with mTOR inhibitors. All previous reported cases present lifesaving effects of mTOR inhibitors in fetuses and neonates with cardiac rhabdomyomas; however, adverse effects cannot be disregarded.
雷帕霉素机制性/哺乳动物靶点（mTOR）抑制剂已成功用于减小心脏横纹肌瘤的大小。然而，已发表的病例数量较少，因此对于治疗方法尚无共识，尤其是关于mTOR抑制剂的给药方案和安全性。基于系统的文献综述和一例新病例报告，我们详细讨论胎儿及新生儿mTOR抑制剂治疗的适应症和不良反应。
在PubMed/MEDLINE和Web of Science上进行全面检索，查找2018年首次报告至2025年7月期间使用相关医学主题词（MeSH）术语和关键词（横纹肌瘤且胎儿或胎儿期或产前且心脏且西罗莫司）组合的研究。如果研究报告了使用mTOR抑制剂治疗怀疑患有胎儿心脏肿瘤和横纹肌瘤的妊娠情况，则纳入研究。
共找到67条结果。排除不合格的出版物后，从15份报告中确定了20例记录在案的病例，均显示mTOR抑制剂对患有心脏横纹肌瘤的胎儿和新生儿具有挽救生命的作用。我们报告了一名产前怀疑患有心脏横纹肌瘤的患者，由于即将出现双侧流出道梗阻，在产前接受了西罗莫司治疗。肿瘤缩小得以实现。由于产妇的医疗原因，产前西罗莫司在5周后不得不停用。产后发生持续性房室折返性心动过速，对电复律或药物复律（胺碘酮）无反应，对依维莫司也无反应。患者在数小时内出现大量毛细血管渗漏综合征。结合限制性心室充盈特性，心动过速导致患者在出生后第七天死亡。
心脏横纹肌瘤有可能成为危及生命的疾病，不仅会损害心肌功能和心脏流出道，还会因肿瘤肌束作为预激综合征的底物导致心律失常，引发宫内或产后房室折返性心动过速，如我们的患者所示。药物治疗方法是对胎儿和新生儿使用mTOR抑制剂。之前所有报告的病例均显示mTOR抑制剂对患有心脏横纹肌瘤的胎儿和新生儿具有挽救生命的作用；然而，不良反应也不容忽视。
