{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:50:00Z","timestamp":1787943000171,"version":"build-2784847793"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T00:00:00Z","timestamp":1745625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Cardiac rhabdomyoma (CR) is the principal cardiac tumor diagnosed in pediatric age and is commonly associated with tuberous sclerosis complex. In some patients, these masses can cause heart failure and difficult-to-control arrhythmias. There are multiple case reports on use of mammalian target of rapamycin (mTOR) inhibitors, everolimus or sirolimus, in treatment of CRs. We reviewed the current data regarding effectiveness of everolimus and sirolimus in treating of CRs in newborns with hemodynamic repercussions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This systematic review was reported according to the PRISMA guidelines. The EBSCO, PubMed, EMBASE, and Lilacs databases were searched for full-text articles reporting the use of everolimus or sirolimus in the treatment of CRs in neonates and infants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty-one articles met inclusion criteria, totaling 48 patients. Hemodynamic instability prompted treatment in 89.5% of cases. Everolimus was used in 83.3% of cases and sirolimus in 16.6%. The median treatment duration was 67 days, with a 57\u2009\u00b1\u200923% average CR size reduction. Common adverse events included hypertriglyceridemia, infections, and hematological abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>mTOR inhibitors appear effective and safe for treating CRs in neonates and infants. The average daily doses were 1.03\u2009mg\/m\u00b2\/day for everolimus and 1.37\u2009mg\/m\u00b2\/day for sirolimus. Randomized controlled clinical trials are necessary to confirm these findings and establish optimal treatment protocols.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Currently, there are no results from randomized clinical trials evaluating the efficacy of mammalian target of rapamycin inhibitors in patients with symptomatic cardiac rhabdomyomas.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This is the first systematic review that evaluates the efficacy and safety of the use of everolimus and sirolimus in the non-surgical treatment of cardiac rhabdomyomas with hemodynamic repercussions in neonates.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Everolimus and sirolimus may be particularly useful in the neonatal period when the hemodynamic complications caused by cardiac rhabdomyomas are more severe.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04043-8","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T12:04:35Z","timestamp":1745669075000},"page":"2045-2057","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Everolimus and sirolimus in the treatment of cardiac rhabdomyomas in neonates"],"prefix":"10.1038","volume":"98","author":[{"given":"Daniel","family":"Hurtado-Sierra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy X.","family":"Ramos Garz\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Romero-Guevara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angie Y.","family":"Serrano-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyda Z.","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"4043_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-11","volume":"2","author":"O Uzun","year":"2007","unstructured":"Uzun, O., Wilson, D. G., Vujanic, G. M., Parsons, J. M. & De Giovanni, J. V. Cardiac tumours in children. Orphanet J. Rare Dis. 2, 11 (2007).","journal-title":"Orphanet J. Rare Dis."},{"key":"4043_CR2","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1007\/s00246-003-0590-4","volume":"25","author":"H Isaacs","year":"2004","unstructured":"Isaacs, H. Fetal and neonatal cardiac tumors. Pediatr. Cardiol. 25, 252\u2013273 (2004).","journal-title":"Pediatr. Cardiol."},{"key":"4043_CR3","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","volume":"123","author":"H Northrup","year":"2021","unstructured":"Northrup, H. et al. Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations. Pediatr. Neurol. 123, 50\u201366 (2021).","journal-title":"Pediatr. Neurol."},{"key":"4043_CR4","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1042\/BJ20080281","volume":"412","author":"J Huang","year":"2008","unstructured":"Huang, J. & Manning, B. D. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J. 412, 179\u2013190 (2008).","journal-title":"Biochem J."},{"key":"4043_CR5","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.114.001493","volume":"3","author":"RB Hinton","year":"2014","unstructured":"Hinton, R. B. et al. Cardiovascular manifestations of tuberous sclerosis complex and summary of the revised diagnostic criteria and surveillance and management recommendations from the International Tuberous Sclerosis Consensus Group. J. Am. Heart Assoc. 3, e001493 (2014).","journal-title":"J. Am. Heart Assoc."},{"key":"4043_CR6","first-page":"8712962","volume":"2016","author":"H Bornaun","year":"2016","unstructured":"Bornaun, H. et al. Regression of cardiac rhabdomyomas in a neonate after Everolimus treatment. Case Rep. Pediatr. 2016, 8712962 (2016).","journal-title":"Case Rep. Pediatr."},{"key":"4043_CR7","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3390\/pediatric13010015","volume":"13","author":"LF Nespoli","year":"2021","unstructured":"Nespoli, L. F. et al. Efficacy of Everolimus low-dose treatment for cardiac Rhabdomyomas in neonatal tuberous sclerosis: case report and literature review. Pediatr. Rep. 13, 104\u2013112 (2021).","journal-title":"Pediatr. Rep."},{"key":"4043_CR8","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jpeds.2017.06.076","volume":"190","author":"N Dahdah","year":"2017","unstructured":"Dahdah, N. Everolimus for the Treatment of Tuberous Sclerosis Complex-Related Cardiac Rhabdomyomas in Pediatric Patients. J. Pediatr. 190, 21\u20136.e7 (2017).","journal-title":"J. Pediatr."},{"key":"4043_CR9","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/pd.825","volume":"24","author":"V Fesslova","year":"2004","unstructured":"Fesslova, V., Villa, L., Rizzuti, T., Mastrangelo, M. & Mosca, F. Natural history and long-term outcome of cardiac rhabdomyomas detected prenatally. Prenat. Diagn. 24, 241\u2013248 (2004).","journal-title":"Prenat. Diagn."},{"key":"4043_CR10","doi-asserted-by":"publisher","first-page":"e1146","DOI":"10.1542\/peds.2006-0504","volume":"118","author":"S J\u00f3\u017awiak","year":"2006","unstructured":"J\u00f3\u017awiak, S. et al. Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex. Pediatrics 118, e1146\u2013e1151 (2006).","journal-title":"Pediatrics"},{"key":"4043_CR11","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1002\/uog.5264","volume":"31","author":"AS Chao","year":"2008","unstructured":"Chao, A. S. et al. Outcome of antenatally diagnosed cardiac rhabdomyoma: case series and a meta-analysis. Ultrasound Obstet. Gynecol. 31, 289\u2013295 (2008).","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"4043_CR12","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1007\/s00246-016-1528-y","volume":"38","author":"F Aw","year":"2017","unstructured":"Aw, F. et al. Accelerated cardiac Rhabdomyoma regression with Everolimus in infants with tuberous Sclerosis complex. Pediatr. Cardiol. 38, 394\u2013400 (2017).","journal-title":"Pediatr. Cardiol."},{"key":"4043_CR13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1017\/S1047951119003147","volume":"30","author":"EV Stelmaszewski","year":"2020","unstructured":"Stelmaszewski, E. V. et al. Everolimus for cardiac rhabdomyomas in children with tuberous sclerosis. The ORACLE study protocol (everOlimus for caRdiac rhAbdomyomas in tuberous sCLErosis): a randomised, multicentre, placebo-controlled, double-blind phase II trial. Cardiol. Young-.-. 30, 337\u2013345 (2020).","journal-title":"Cardiol. Young-.-."},{"key":"4043_CR14","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1177\/2150135118822711","volume":"12","author":"A Garg","year":"2021","unstructured":"Garg, A., Gorla, S. R., Kardon, R. E. & Swaminathan, S. Rapid Involution of Large Cardiac Rhabdomyomas With Everolimus Therapy. World J. Pediatr. Congenit. Heart Surg. 12, 426\u2013429 (2021).","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"4043_CR15","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/ped.12816","volume":"58","author":"SG Hoshal","year":"2016","unstructured":"Hoshal, S. G., Samuel, B. P., Schneider, J. R., Mammen, L. & Vettukattil, J. J. Regression of massive cardiac rhabdomyoma on everolimus therapy. Pediatr. Int. 58, 397\u2013399 (2016).","journal-title":"Pediatr. Int."},{"key":"4043_CR16","doi-asserted-by":"publisher","first-page":"4907","DOI":"10.3390\/ijerph18094907","volume":"18","author":"M Sugalska","year":"2021","unstructured":"Sugalska, M., Tomik, A., J\u00f3\u017awiak, S. & Werner, B. Treatment of cardiac Rhabdomyomas with mTOR inhibitors in children with tuberous Sclerosis complex-a systematic review. Int J. Environ. Res Public Health 18, 4907 (2021).","journal-title":"Int J. Environ. Res Public Health"},{"key":"4043_CR17","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1016\/j.athoracsur.2015.06.030","volume":"100","author":"X Liu","year":"2015","unstructured":"Liu, X. et al. Treatment strategies for primary tumors of the heart in children: a 10-year experience. Ann. Thorac. Surg. 100, 1744\u20131749 (2015).","journal-title":"Ann. Thorac. Surg."},{"key":"4043_CR18","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S0140-6736(12)61134-9","volume":"381","author":"DN Franz","year":"2013","unstructured":"Franz, D. N. et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 381, 125\u2013132 (2013).","journal-title":"Lancet"},{"key":"4043_CR19","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/S0140-6736(12)61767-X","volume":"381","author":"JJ Bissler","year":"2013","unstructured":"Bissler, J. J. et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 381, 817\u2013824 (2013).","journal-title":"Lancet"},{"key":"4043_CR20","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s40272-019-00337-7","volume":"21","author":"M Bevacqua","year":"2019","unstructured":"Bevacqua, M. et al. Off-Label use of Sirolimus and Everolimus in a pediatric center: a case series and review of the literature. Paediatr. Drugs 21, 185\u2013193 (2019).","journal-title":"Paediatr. Drugs"},{"key":"4043_CR21","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","volume":"372","author":"MJ Page","year":"2021","unstructured":"Page, M. J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372, n71 (2021).","journal-title":"BMJ"},{"key":"4043_CR22","unstructured":"Moola, S. et al. Systematic reviews of etiology and risk (2020). In JBI Manual for Evidence Synthesis (Aromataris, E., Lockwood, C., Porritt, K., Pilla, B. & Jordan, Z., eds) https:\/\/synthesismanual.jbi.global (JBI, 2024)."},{"key":"4043_CR23","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.1016\/S0140-6736(16)31419-2","volume":"388","author":"JA French","year":"2016","unstructured":"French, J. A. et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet 388, 2153\u20132163 (2016).","journal-title":"Lancet"},{"key":"4043_CR24","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1017\/S104795112000147X","volume":"30","author":"A Cleary","year":"2020","unstructured":"Cleary, A. & McMahon, C. J. Literature review of international mammalian target of rapamycin inhibitor use in the non-surgical management of haemodynamically significant cardiac rhabdomyomas. Cardiol. Young-.-. 30, 923\u2013933 (2020).","journal-title":"Cardiol. Young-.-."},{"key":"4043_CR25","doi-asserted-by":"publisher","first-page":"S124","DOI":"10.1016\/j.ejps.2017.05.037","volume":"109S","author":"T Mizuno","year":"2017","unstructured":"Mizuno, T. et al. Model-based precision dosing of sirolimus in pediatric patients with vascular anomalies. Eur. J. Pharm. Sci. 109S, S124\u2013S131 (2017).","journal-title":"Eur. J. Pharm. Sci."},{"key":"4043_CR26","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1007\/s00246-024-03420-0","volume":"45","author":"LY Ng","year":"2024","unstructured":"Ng, L. Y. et al. Cardiac Rhabdomyomas presenting with critical cardiac obstruction in neonates and infants: treatment strategies and outcome, a single-center experience. Pediatr. Cardiol. 45, 1132\u20131141 (2024).","journal-title":"Pediatr. Cardiol."},{"key":"4043_CR27","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.pharmthera.2012.12.007","volume":"138","author":"UM Zanger","year":"2013","unstructured":"Zanger, U. M. & Schwab, M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharm. Ther. 138, 103\u2013141 (2013).","journal-title":"Pharm. Ther."},{"key":"4043_CR28","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/jbt.20179","volume":"21","author":"RN Hines","year":"2007","unstructured":"Hines, R. N. Ontogeny of human hepatic cytochromes P450. J. Biochem Mol. Toxicol. 21, 169\u2013175 (2007).","journal-title":"J. Biochem Mol. Toxicol."},{"key":"4043_CR29","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/psp4.12096","volume":"5","author":"C Emoto","year":"2016","unstructured":"Emoto, C. et al. Characterizing the developmental trajectory of sirolimus clearance in neonates and infants. CPT Pharmacomet. Syst. Pharm. 5, 411\u2013417 (2016).","journal-title":"CPT Pharmacomet. Syst. Pharm."},{"key":"4043_CR30","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1093\/neuonc\/nov152","volume":"17","author":"JP MacKeigan","year":"2015","unstructured":"MacKeigan, J. P. & Krueger, D. A. Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of tuberous sclerosis complex. Neuro Oncol. 17, 1550\u20131559 (2015).","journal-title":"Neuro Oncol."},{"key":"4043_CR31","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1513\/AnnalsATS.201605-335OC","volume":"13","author":"T Takada","year":"2016","unstructured":"Takada, T. et al. Efficacy and safety of long-term Sirolimus Therapy for Asian patients with Lymphangioleiomyomatosis. Ann. Am. Thorac. Soc. 13, 1912\u20131922 (2016).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"4043_CR32","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.jpeds.2016.01.027","volume":"172","author":"S J\u00f3\u017awiak","year":"2016","unstructured":"J\u00f3\u017awiak, S., Kotulska, K., Berkowitz, N., Brechenmacher, T. & Franz, D. N. Safety of Everolimus in Patients Younger than 3 Years of Age: Results from EXIST-1, a Randomized, Controlled Clinical Trial. J. Pediatr. 172, 151\u2013155.e1 (2016).","journal-title":"J. Pediatr."},{"key":"4043_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1077-6","volume":"14","author":"A Saffari","year":"2019","unstructured":"Saffari, A. et al. Safety and efficacy of mTOR inhibitor treatment in patients with tuberous sclerosis complex under 2\u2009years of age - a multicenter retrospective study. Orphanet J. Rare Dis. 14, 96 (2019).","journal-title":"Orphanet J. Rare Dis."},{"key":"4043_CR34","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.ad.2019.05.009","volume":"112","author":"A Freites-Martinez","year":"2021","unstructured":"Freites-Martinez, A., Santana, N., Arias-Santiago, S. & Viera, A. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to evaluate the severity of adverse events of anticancer therapies. Actas Dermosifiliogr. (Engl. Ed.). 112, 90\u201392 (2021).","journal-title":"Actas Dermosifiliogr. (Engl. Ed.)."},{"key":"4043_CR35","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.3390\/children9091295","volume":"9","author":"Z Zhang","year":"2022","unstructured":"Zhang, Z. et al. Safety Evaluation of Oral Sirolimus in the treatment of childhood diseases: a systematic review. Children 9, 1295 (2022).","journal-title":"Children"},{"key":"4043_CR36","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1016\/j.ejpn.2018.06.007","volume":"22","author":"DA Krueger","year":"2018","unstructured":"Krueger, D. A. et al. Short-term safety of mTOR inhibitors in infants and very young children with tuberous sclerosis complex (TSC): Multicentre clinical experience. Eur. J. Paediatr. Neurol. 22, 1066\u20131073 (2018).","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"4043_CR37","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.pharep.2016.01.005","volume":"68","author":"K Sadowski","year":"2016","unstructured":"Sadowski, K., Kotulska, K. & J\u00f3\u017awiak, S. Management of side effects of mTOR inhibitors in tuberous sclerosis patients. Pharm. Rep. 68, 536\u2013542 (2016).","journal-title":"Pharm. Rep."},{"key":"4043_CR38","doi-asserted-by":"publisher","first-page":"e243","DOI":"10.1542\/peds.2011-3476","volume":"130","author":"HA Demir","year":"2012","unstructured":"Demir, H. A., Ekici, F., Yazal Erdem, A., Emir, S. & Tun\u00e7, B. Everolimus: a challenging drug in the treatment of multifocal inoperable cardiac rhabdomyoma. Pediatrics 130, e243\u2013e247 (2012).","journal-title":"Pediatrics"},{"key":"4043_CR39","doi-asserted-by":"publisher","first-page":"e1199","DOI":"10.1542\/peds.2013-3293","volume":"134","author":"C Breathnach","year":"2014","unstructured":"Breathnach, C., Pears, J., Franklin, O., Webb, D. & McMahon, C. J. Rapid regression of left ventricular outflow tract rhabdomyoma after sirolimus therapy. Pediatrics 134, e1199\u2013e1202 (2014).","journal-title":"Pediatrics"},{"key":"4043_CR40","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.pediatrneurol.2015.01.004","volume":"52","author":"I Goyer","year":"2015","unstructured":"Goyer, I., Dahdah, N. & Major, P. Use of mTOR inhibitor everolimus in three neonates for treatment of tumors associated with tuberous sclerosis complex. Pediatr. Neurol. 52, 450\u2013453 (2015).","journal-title":"Pediatr. Neurol."},{"key":"4043_CR41","doi-asserted-by":"crossref","unstructured":"Wagner, R. et al. Oral everolimus for treatment of a giant left ventricular rhabdomyoma in a neonate-rapid tumor regression documented by real time 3D Echocardiography. Echocardiography 32, 1876\u20131879 (2015).","DOI":"10.1111\/echo.13015"},{"key":"4043_CR42","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1017\/S1047951116000421","volume":"26","author":"M Colaneri","year":"2016","unstructured":"Colaneri, M., Quarti, A. & Pozzi, M. Everolimus-induced near-resolution of giant cardiac rhabdomyomas and large renal angiomyolipoma in a newborn with tuberous sclerosis complex. Cardiol. Young. 26, 1025\u20131028 (2016).","journal-title":"Cardiol. Young."},{"key":"4043_CR43","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1007\/s00246-017-1688-4","volume":"38","author":"JS Chang","year":"2017","unstructured":"Chang, J. S., Chiou, P. Y., Yao, S. H., Chou, I. C. & Lin, C. Y. Regression of neonatal cardiac Rhabdomyoma in two months through low-dose Everolimus therapy: a report of three cases. Pediatr. Cardiol. 38, 1478\u20131484 (2017).","journal-title":"Pediatr. Cardiol."},{"key":"4043_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000460813","volume":"2","author":"SJ Lee","year":"2017","unstructured":"Lee, S. J. et al. Rapid regression of obstructive cardiac Rhabdomyoma in a preterm neonate after Sirolimus Therapy. Biomed. Hub. 2, 1\u20136 (2017).","journal-title":"Biomed. Hub."},{"key":"4043_CR45","doi-asserted-by":"publisher","first-page":"20160067","DOI":"10.1515\/crpm-2016-0067","volume":"6","author":"M Schmidt-Fittschen","year":"2017","unstructured":"Schmidt-Fittschen, M., Spahn, S., Al Naimi, A., Schranz, D. & Bahlmann, F. Everolimus treatment of a fetal intracardiac rhabdomyoma not associated with the tuberous sclerosis complex: a case report. Case Rep. Perinat. Med. 6, 20160067 (2017).","journal-title":"Case Rep. Perinat. Med."},{"key":"4043_CR46","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1017\/S1047951118000598","volume":"28","author":"A Mart\u00ednez-Garc\u00eda","year":"2018","unstructured":"Mart\u00ednez-Garc\u00eda, A. et al. Giant left ventricular rhabdomyoma treated successfully with everolimus: case report and review of literature. Cardiol. Young. 28, 903\u2013909 (2018).","journal-title":"Cardiol. Young."},{"key":"4043_CR47","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1017\/S104795111700244X","volume":"28","author":"MD Weiland","year":"2018","unstructured":"Weiland, M. D., Bonello, K. & Hill, K. D. Rapid regression of large cardiac rhabdomyomas in neonates after sirolimus therapy. Cardiol. Young. 28, 485\u2013489 (2018).","journal-title":"Cardiol. Young."},{"key":"4043_CR48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.4103\/apc.APC_79_18","volume":"12","author":"B Dhulipudi","year":"2019","unstructured":"Dhulipudi, B., Bhakru, S., Rajan, S., Doraiswamy, V. & Koneti, N. R. Symptomatic improvement using everolimus in infants with cardiac rhabdomyoma. Ann. Pediatr. Cardiol. 12, 45\u201348 (2019).","journal-title":"Ann. Pediatr. Cardiol."},{"key":"4043_CR49","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.jaccas.2019.07.030","volume":"1","author":"C Lawley","year":"2019","unstructured":"Lawley, C., Popat, H., Wong, M., Badawi, N. & Ayer, J. A dramatic response to Sirolimus Therapy in a premature infant with massive cardiac Rhabdomyoma. JACC Case Rep. 1, 327\u2013331 (2019).","journal-title":"JACC Case Rep."},{"key":"4043_CR50","doi-asserted-by":"publisher","first-page":"e213","DOI":"10.1055\/s-0039-1692198","volume":"9","author":"Y Shibata","year":"2019","unstructured":"Shibata, Y. et al. Effect and complications of Everolimus use for giant cardiac Rhabdomyomas with neonatal tuberous sclerosis. AJP Rep. 9, e213\u2013e217 (2019).","journal-title":"AJP Rep."},{"key":"4043_CR51","doi-asserted-by":"crossref","first-page":"208","DOI":"10.18233\/APM41No5pp208-2141962","volume":"41","author":"M Esmer-S\u00e1nchez","year":"2020","unstructured":"Esmer-S\u00e1nchez, M. et al. Everolimus response in a newborn with cardiac rhabdomyoma associated to tuberous sclerosis complex: Case report. Acta Pediatr. Mex. 41, 208\u2013214 (2020).","journal-title":"Acta Pediatr. Mex."},{"key":"4043_CR52","first-page":"142","volume":"4","author":"K Prasad","year":"2020","unstructured":"Prasad, K. et al. Accelerated regression of cardiac rhabdomyoma by mTOR inhibitors in a neonate with heart failure: A case report. IHJ Cardiovasc. Case Rep. (CVCR) 4, 142\u2013145 (2020).","journal-title":"IHJ Cardiovasc. Case Rep. (CVCR)"},{"key":"4043_CR53","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1017\/S1047951121000639","volume":"31","author":"M \u00c7etin","year":"2021","unstructured":"\u00c7etin, M., Ayd\u0131n, A. A. & Karaman, K. Everolimus treatment in a 3-month-old infant with tuberous sclerosis complex cardiac rhabdomyoma, severe left ventricular outflow tract obstruction, and hearing loss. Cardiol. Young. 31, 1359\u20131362 (2021).","journal-title":"Cardiol. Young."},{"key":"4043_CR54","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1017\/S1047951120003819","volume":"31","author":"Y Nir-David","year":"2021","unstructured":"Nir-David, Y., Brosilow, S. & Khoury, A. Rapid response of a cardiac rhabdomyoma causing severe right ventricular outflow obstruction to Sirolimus in an infant with negative genetics for Tuberous sclerosis. Cardiol. Young. 31, 312\u2013314 (2021).","journal-title":"Cardiol. Young."},{"key":"4043_CR55","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1016\/j.jaccas.2021.07.013","volume":"3","author":"J Relan","year":"2021","unstructured":"Relan, J. et al. Prenatal Pericardiocentesis and Postnatal Sirolimus for a Giant Inoperable Cardiac Rhabdomyoma. JACC Case Rep. 3, 1473\u20131479 (2021).","journal-title":"JACC Case Rep."},{"key":"4043_CR56","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1002\/ajmg.a.62120","volume":"185","author":"MP Silva-S\u00e1nchez","year":"2021","unstructured":"Silva-S\u00e1nchez, M. P. et al. Everolimus for severe arrhythmias in tuberous sclerosis complex related cardiac rhabdomyomas. Am. J. Med. Genet. A 185, 1525\u20131531 (2021).","journal-title":"Am. J. Med. Genet. A"},{"key":"4043_CR57","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1111\/ped.14472","volume":"63","author":"T Tsuchihashi","year":"2021","unstructured":"Tsuchihashi, T., Tsuno, Y., Kakimoto, N., Riko, M. & Kumagai, T. Use of everolimus for cardiac rhabdomyomas in a very-low-birthweight infant. Pediatr. Int. 63, 726\u2013727 (2021).","journal-title":"Pediatr. Int."},{"key":"4043_CR58","doi-asserted-by":"publisher","first-page":"141","DOI":"10.5152\/AnatolJCardiol.2021.60","volume":"26","author":"M Beyazal","year":"2022","unstructured":"Beyazal, M., \u00d6zyaz\u0131c\u0131, A. & Ye\u015fil, \u015e Multiple intracardiac benign tumors treated with low-dose everolimus. Anatol. J. Cardiol. 26, 141\u2013142 (2022).","journal-title":"Anatol. J. Cardiol."},{"key":"4043_CR59","doi-asserted-by":"publisher","first-page":"e15188","DOI":"10.1111\/ped.15188","volume":"64","author":"N \u00c7etiner","year":"2022","unstructured":"\u00c7etiner, N., Kavas, N. & K\u00fc\u00e7\u00fckosmano\u011flu, O. Rapid regression everolimus therapy in a neonate with cardiac rhabdomyoma. Pediatr. Int. 64, e15188 (2022).","journal-title":"Pediatr. Int."},{"key":"4043_CR60","doi-asserted-by":"publisher","first-page":"e15219","DOI":"10.1111\/ped.15219","volume":"64","author":"S Inoue","year":"2022","unstructured":"Inoue, S., Inuzuka, R., Kakiuchi, S., Sato, A. & Matsui, H. Successful treatment with everolimus for severe heart failure with large cardiac rhabdomyomas. Pediatr. Int. 64, e15219 (2022).","journal-title":"Pediatr. Int."},{"key":"4043_CR61","doi-asserted-by":"publisher","first-page":"58","DOI":"10.4103\/apc.apc_11_21","volume":"15","author":"E Sagiv","year":"2022","unstructured":"Sagiv, E., Chikkabyrappa, S. M., Conwell, J., Lewin, M. & Chun, T. U. H. Use of Everolimus to treat cardiac rhabdomyomas and incessant arrhythmias in a newborn: Benefits and complications. Ann. Pediatr. Cardiol. 15, 58\u201360 (2022).","journal-title":"Ann. Pediatr. Cardiol."},{"key":"4043_CR62","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.case.2022.03.009","volume":"6","author":"C Winkie","year":"2022","unstructured":"Winkie, C., Gelman, J., Verhoeven, P. & Chaudhuri, N. R. Sirolimus-induced regression of Tuberous Sclerosis-associated cardiac Rhabdomyoma causing left ventricular outflow tract obstruction. CASE 6, 361\u2013365 (2022).","journal-title":"CASE"},{"key":"4043_CR63","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1017\/S1047951123000094","volume":"33","author":"K Babao\u011flu","year":"2023","unstructured":"Babao\u011flu, K., Ba\u015far, E. Z., Usta, E., Y\u0131lmaz, E. H. & G\u00fcnlemez, A. Effect of different dose regimens of everolimus in a series of neonates with giant cardiac rhabdomyomas. Cardiol. Young. 33, 2291\u20132296 (2023).","journal-title":"Cardiol. Young."},{"key":"4043_CR64","doi-asserted-by":"publisher","first-page":"1109646","DOI":"10.3389\/fped.2023.1109646","volume":"11","author":"D Hurtado-Sierra","year":"2023","unstructured":"Hurtado-Sierra, D., Ramos Garz\u00f3n, J. X., Rojas, L. Z., Fern\u00e1ndez-G\u00f3mez, O. & Manrique-Rinc\u00f3n, F. Case report: Accelerated regression of giant cardiac rhabdomyomas in neonates with low dose everolimus. Front. Pediatr. 11, 1109646 (2023).","journal-title":"Front. Pediatr."},{"key":"4043_CR65","doi-asserted-by":"crossref","unstructured":"Montaguti, E. et al. A case of massive fetal cardiac rhabdomyoma: ultrasound features and management. J. Matern. Fetal Neonatal Med. 36, 2197099 (2023).","DOI":"10.1080\/14767058.2023.2197099"}],"container-title":["Pediatric Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04043-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04043-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04043-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:03:20Z","timestamp":1768554200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41390-025-04043-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,26]]},"references-count":65,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["4043"],"URL":"https:\/\/doi.org\/10.1038\/s41390-025-04043-8","relation":{},"ISSN":["0031-3998","1530-0447"],"issn-type":[{"value":"0031-3998","type":"print"},{"value":"1530-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,26]]},"assertion":[{"value":"11 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}