SYSTEMATIC REVIEW article
Front. Pediatr.
Sec. Obstetric and Pediatric Pharmacology
Volume 13 - 2025 | doi: 10.3389/fped.2025.1649341
Drug review: mTOR-inhibitor therapy in fetal cardiac rhabdomyoma -a tightrope walk
Provisionally accepted
Nadine Muschel
Michaela HöckElke GriesmaierSamira Abdel AzimElisabeth Ralser
Christina SchreinerElisabeth Schermer
Ursula Kiechl-Kohlendorfer
Irene Mutz-Dehbalaie
Miriam Michel*- Innsbruck Medical University, Innsbruck, Austria
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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 indication and adverse effects of fetal and neonatal mTOR-inhibitor therapy.Comprehensive search 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.67 results were found. After exclusion of non-eligible publications, a total of 20 documented cases were identified from 15 reports, all of those 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 was -due to imminent bilateral outflow tract obstruction -prenatally treated with sirolimus. Tumour regression could be achieved. For maternal medical reasons, after 5 weeks prenatal sirolimus had to be stopped. Postnatal incessant atrioventricular reentrant tachycardia occurred, unresponsive to electric or medical cardioversion (amiodarone), and unresponsive to everolimus. Within hours the patient developed massive capillary leak syndrome. In combination with restrictive ventricular filling properties, the tachycardia turned out lethal 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 tumour muscle bundles as substrate for a preexcitation syndrome resulting in intrauterine or postnatal atrioventricular reentrant tachycardia, as observed in our patient. The pharmacological therapeutic
Keywords: adverse effects, fetal cardiac tumour, Rhabdomyoma, Sirolimus, Reentry tachycardia
Received: 18 Jun 2025; Accepted: 22 Jul 2025.
Copyright: © 2025 Muschel, Höck, Griesmaier, Azim, Ralser, Schreiner, Schermer, Kiechl-Kohlendorfer, Mutz-Dehbalaie and Michel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Miriam Michel, Innsbruck Medical University, Innsbruck, Austria
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